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The origin and evolution of cell types

Nature Reviews Genetics volume 17, pages 744–757 (2016)Cite this article

Subjects

Key Points

  • A new evolutionary definition of cell types is presented. Cell types are evolutionary units defined by common descent rather than phenotypic similarity, and characterized by their ability to evolve gene expression programmes independently of each other.

  • The evolutionary diversification of cell types is driven by genomic individuation, which increases the capacity of sister cell types to establish and maintain distinct gene expression programmes.

  • Core regulatory complexes (CoRCs) of terminal selectors determine cell type identity. CoRCs are the molecular agents that enable cell type-specific gene expression.

  • Apomeres are new cellular modules or variants of modules in incipient sister cell types that implement cell type-specific structure and functions.

  • Concerted evolution is characteristic for related cell types that share some genomic information, such as genes or shared enhancers.

  • The evolutionary lineage of cell type individuation is different from the developmental lineage. Serial sister cell types that develop from distinct developmental regions are closely related in evolution but differ in developmental lineage.

Abstract

Cell types are the basic building blocks of multicellular organisms and are extensively diversified in animals. Despite recent advances in characterizing cell types, classification schemes remain ambiguous. We propose an evolutionary definition of a cell type that allows cell types to be delineated and compared within and between species. Key to cell type identity are evolutionary changes in the 'core regulatory complex' (CoRC) of transcription factors, that make emergent sister cell types distinct, enable their independent evolution and regulate cell type-specific traits termed apomeres. We discuss the distinction between developmental and evolutionary lineages, and present a roadmap for future research.

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Figure 1: Evolution of phenotypic similarity.
Figure 2: The regulatory signature of cell type identity.
Figure 3: Sister cell types evolve by individuation.
Figure 4: Evolution of pre- and postsynaptic apomeres by module integration and divergence.
Figure 5: Interrelationship of developmental and evolutionary cell type lineages.

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References

  1. Valentine, J. W. in Keywords and Concepts in Evolutionary Developmental Biology (eds Hall, B. K. & Olson, W. M.) 35–53 (Harvard Univ. Press, 2003).

    Google Scholar 

  2. Kepecs, A. & Fishell, G. Interneuron cell types are fit to function. Nature 505, 318–326 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Stegle, O., Teichmann, S. A. & Marioni, J. C. Computational and analytical challenges in single-cell transcriptomics. Nat. Rev. Genet. 16, 133–145 (2015).

    Article  CAS  PubMed  Google Scholar 

  4. Shapiro, E., Biezuner, T. & Linnarsson, S. Single-cell sequencing-based technologies will revolutionize whole-organism science. Nat. Rev. Genet. 14, 618–630 (2013).

    Article  CAS  PubMed  Google Scholar 

  5. Schwartzman, O. & Tanay, A. Single-cell epigenomics: techniques and emerging applications. Nat. Rev. Genet. 16, 716–726 (2015).

    Article  CAS  PubMed  Google Scholar 

  6. Alberts, B. The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell 92, 291–294 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. Hartwell, L. H., Hopfield, J. J., Leibler, S. & Murray, A. W. From molecular to modular cell biology. Nature 402, C47–C52 (1999).

    Article  CAS  PubMed  Google Scholar 

  8. Pereira-Leal, J. B., Levy, E. D. & Teichmann, S. A. The origins and evolution of functional modules: lessons from protein complexes. Phil. Trans. R. Soc. B 361, 507–517 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pereira-Leal, J. B., Levy, E. D., Kamp, C. & Teichmann, S. A. Evolution of protein complexes by duplication of homomeric interactions. Genome Biol. 8, R51 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Achim, K. & Arendt, D. Structural evolution of cell types by step-wise assembly of cellular modules. Curr. Opin. Genet. Dev. 27, 102–108 (2014).

    Article  CAS  PubMed  Google Scholar 

  11. Vickaryous, M. K. & Hall, B. K. Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest. Biol. Rev. 81, 425–455 (2006).The first account of human cell type diversity constructed through the lens of evolution.

    Article  PubMed  Google Scholar 

  12. Musser, J. M. & Wagner, G. P. Character trees from transcriptome data: origin and individuation of morphological characters and the so-called 'species signal'. J. Exp. Zool. 324, 588–604 (2015).Introduces the phenomenon of concerted transcriptome evolution and shows how it influences the comparison of cell type transcriptomes across species.

    Article  CAS  Google Scholar 

  13. Valentine, J. W., Collins, A. G. & Meyer, C. P. Morphological complexity increase in metazoans. Paleobiology 20, 131–142 (1994).

    Article  Google Scholar 

  14. Wagner, G. P., Kin, K., Muglia, L. & Pavli, M. Evolution of mammalian pregnancy and the origin of the decidual stromal cell. Int. J. Dev. Biol. 58, 117–126 (2014).

    Article  CAS  PubMed  Google Scholar 

  15. Schlosser, G. Modularity and the units of evolution. Theory Biosci. 121, 1–80 (2002).

    Article  Google Scholar 

  16. Wagner, G. P. & Lynch, V. J. Evolutionary novelties. Curr. Biol. 20, R48–R52 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. Wagner, G. P. Homology, Genes, And Evolutionary Innovation (Princeton Univ. Press, 2014).A modern account of the molecular underpinnings of homology and evolutionary novelty.

    Book  Google Scholar 

  18. Pavlicev, M., Wagner, G. P., Noonan, J. P., Hallgrimsson, B. & Cheverud, J. M. Genomic correlates of relationship QTL involved in fore- versus hind limb divergence in mice. Genome Biol. Evol. 5, 1926–1936 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Arendt, D. The evolution of cell types in animals: emerging principles from molecular studies. Nat. Rev. Genet. 9, 868–882 (2008).Introduces the sister cell type model for the origin of novel cell types and sets the stage for an evolutionary perspective on the cell type concept.

    Article  CAS  PubMed  Google Scholar 

  20. Serb, J. M. & Oakley, T. H. Hierarchical phylogenetics as a quantitative analytical framework for evolutionary developmental biology. Bioessays 27, 1158–1166 (2005).Shows how phylogenetic tools can be used to track the history and interrelationships of cell types and other organismal parts.

    Article  CAS  PubMed  Google Scholar 

  21. Arendt, D. Evolution of eyes and photoreceptor cell types. Int. J. Dev. Biol. 47, 563–571 (2003).

    PubMed  Google Scholar 

  22. Brunet, T. et al. The evolutionary origin of bilaterian smooth and striated myocytes. Preprint at bioRxiv http://dx.doi.org/10.1101/064881 (2016).

  23. Graf, T. & Enver, T. Forcing cells to change lineages. Nature 462, 587–594 (2009).A pioneering paper that suggests that the gene regulatory network underlying cell type identity has a flat hierarchy with a few transcription factor genes controlling many downstream effector genes.

    Article  CAS  PubMed  Google Scholar 

  24. Hobert, O. Regulatory logic of neuronal diversity: terminal selector genes and selector motifs. Proc. Natl Acad. Sci. USA 105, 20067–20071 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Saint-André, V. et al. Models of human core transcriptional regulatory circuitries. Genome Res. 26, 385–396 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Young, R. A. Control of the embryonic stem cell state. Cell 144, 940–954 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Flames, N. & Hobert, O. Gene regulatory logic of dopamine neuron differentiation. Nature 458, 885–889 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hobert, O. Regulation of terminal differentiation programs in the nervous system. Annu. Rev. Cell Dev. Biol. 27, 681–696 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Oosterveen, T. et al. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals. Proc. Natl Acad. Sci. USA 110, 7330–7335 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mullen, A. C. et al. Master transcription factors determine cell-type-specific responses to TGF-ß signaling. Cell 147, 565–576 (2011).Demonstrates empirically that cell type terminal selectors are responsible for mediating the cell type-specific response to a common cellular signal.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Trompouki, E. et al. Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration. Cell 147, 577–589 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Erwin, D. & Davidson, E. The evolution of hierarchical gene regulatory networks. Nat. Rev. Genet. 10, 141–148 (2009).

    Article  CAS  PubMed  Google Scholar 

  33. Deneris, E. S. & Hobert, O. Maintenance of postmitotic neuronal cell identity. Nat. Neurosci. 17, 899–907 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Davis, R. L., Weintraub, H. & Lassar, A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987–1000 (1987).

    Article  CAS  PubMed  Google Scholar 

  35. Arlotta, P. & Hobert, O. Homeotic transformations of neuronal cell identities. Trends Neurosci. 38, 751–762 (2015).

    Article  CAS  PubMed  Google Scholar 

  36. Hobert, O. Terminal selectors of neuronal identity. Curr. Top. Dev. Biol. 116, 455–475 (2016).Outlines the important role of terminal selector genes in establishing and maintaining cell type identity.

    Article  CAS  PubMed  Google Scholar 

  37. Lee, S. et al. A regulatory network to segregate the identity of neuronal subtypes. Dev. Cell 14, 877–889 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Duggan, A., Ma, C. & Chalfie, M. Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes. Development 125, 4107–4119 (1998).

    Article  CAS  PubMed  Google Scholar 

  39. Rudra, D. et al. Transcription factor Foxp3 and its protein partners form a complex regulatory network. Nat. Immunol. 13, 1010–1019 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gordon, P. M. & Hobert, O. A competition mechanism for a homeotic neuron identity transformation in C. elegans. Dev. Cell 34, 206–219 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Jin, Z. et al. Different transcription factors regulate nestin gene expression during P19 cell neural differentiation and central nervous system development. J. Biol. Chem. 284, 8160–8173 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lodato, M. A. et al. SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state. PLoS Genet. 9, e1003288 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sokolik, C. et al. Transcription factor competition allows embryonic stem cells to distinguish authentic signals from noise. Cell Syst. 1, 117–129 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Joshi, K., Lee, S., Lee, B., Lee, J. W. & Lee, S.-K. LMO4 controls the balance between excitatory and inhibitory spinal V2 interneurons. Neuron 61, 839–851 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Henke, R. M. et al. Neurog2 is a direct downstream target of the Ptf1a–Rbpj transcription complex in dorsal spinal cord. Development 136, 2945–2954 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Borromeo, M. D. et al. A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord. Development 141, 3102–3102 (2014).

    Article  CAS  PubMed Central  Google Scholar 

  47. He, M. et al. Cell-type-based analysis of microRNA profiles in the mouse brain. Neuron 73, 35–48 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hobert, O. Gene regulation by transcription factors and microRNAs. Science 319, 1785–1786 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Jovic˘ic´, A. et al. Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes. J. Neurosci. 33, 5127–5137 (2013).

    Article  CAS  Google Scholar 

  50. Poole, R. J. & Hobert, O. Early embryonic programming of neuronal left/right asymmetry in C. elegans. Curr. Biol. 16, 2279–2292 (2006).

    Article  CAS  PubMed  Google Scholar 

  51. Kent, O. A., McCall, M. N., Cornish, T. C. & Halushka, M. K. Lessons from miR-143/145: the importance of cell-type localization of miRNAs. Nucleic Acids Res. 42, 7528–7538 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Irimia, M. et al. A highly conserved program of neuronal microexons is misregulated in autistic brains. Cell 159, 1511–1523 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Charlet-B, N., Logan, P., Singh, G. & Cooper, T. A. Dynamic antagonism between ETR-3 and PTB regulates cell type-specific alternative splicing. Mol. Cell 9, 649–658 (2002).

    Article  CAS  PubMed  Google Scholar 

  54. Feng, Y. et al. SRp38 regulates alternative splicing and is required for Ca2+ handling in the embryonic heart. Dev. Cell 16, 528–538 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chen, M. & Manley, J. L. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat. Rev. Mol. Cell Biol. 10, 741–754 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Giampietro, C. et al. The alternative splicing factor Nova2 regulates vascular development and lumen formation. Nat. Commun. 6, 8479 (2015).

    Article  CAS  PubMed  Google Scholar 

  57. Lauri, A. et al. Development of the annelid axochord: insights into notochord evolution. Science 345, 1365–1368 (2014).

    Article  CAS  PubMed  Google Scholar 

  58. Lamb, T. D. Evolution of phototransduction, vertebrate photoreceptors and retina. Prog. Retin. Eye Res. 36, 52–119 (2013).

    Article  CAS  PubMed  Google Scholar 

  59. Gellersen, B. & Brosens, J. J. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr. Rev. 35, 851–905 (2014).

    Article  CAS  PubMed  Google Scholar 

  60. Emera, D., Romero, R. & Wagner, G. The evolution of menstruation: a new model for genetic assimilation. Bioessays 34, 26–35 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Kin, K., Nnamani, M. C., Lynch, V. J., Michaelides, E. & Wagner, G. P. Cell-type phylogenetics and the origin of endometrial stromal cells. Cell Rep. 10, 1398–1409 (2015).

    Article  CAS  PubMed  Google Scholar 

  62. Mess, A. & Carter, A. M. Evolutionary transformations of fetal membrane characters in Eutheria with special reference to Afrotheria. J. Exp. Zool. 306, 140–163 (2006).

    Article  Google Scholar 

  63. Chavan, A. R., Bhullar, B.-A. S. & Wagner, G. P. What was the ancestral function of decidual stromal cells? A model for the evolution of eutherian pregnancy. Placenta 40, 40–51 (2016).

    Article  PubMed  Google Scholar 

  64. Lynch, V. J., Brayer, K., Gellersen, B. & Wagner, G. P. HoxA-11 and FOXO1A cooperate to regulate decidual prolactin expression: towards inferring the core transcriptional regulators of decidual genes. PLoS ONE 4, e6845 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Kao, L. C. et al. Global gene profiling in human endometrium during the window of implantation. Endocrinology 143, 2119–2138 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Eda Akbas, G., Song, J. & Taylor, H. S. A HOXA10 estrogen response element (ERE) is differentially regulated by 17 beta-estradiol and diethylstilbestrol (DES). J. Mol. Biol. 340, 1013–1023 (2004).

    Article  PubMed  CAS  Google Scholar 

  67. Sarno, J. L., Kliman, H. J. & Taylor, H. S. HOXA10, Pbx2, and Meis1 protein expression in the human endometrium: formation of multimeric complexes on HOXA10 target genes. J. Clin. Endocrinol. Metab. 90, 522–528 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Wetendorf, M. & DeMayo, F. J. The progesterone receptor regulates implantation, decidualization, and glandular development via a complex paracrine signaling network. Mol. Cell. Endocrinol. 357, 108–118 (2012).

    Article  CAS  PubMed  Google Scholar 

  69. Lynch, V. J. et al. Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals. Proc. Natl Acad. Sci. USA 105, 14928–14933 (2008).Reconstructs ancestral transcription factors to show the importance of transcription factor protein-coding changes for cell type evolution.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lynch, V. J., May, G. & Wagner, G. P. Regulatory evolution through divergence of a phosphoswitch in the transcription factor CEBPB. Nature 480, 383–386 (2012).

    Article  CAS  Google Scholar 

  71. Nnamani, M. C. et al. A derived allosteric switch underlies the evolution of conditional cooperativity between HOXA11 and FOXO1. Cell Rep. 15, 2097–2108 (2016).

    Article  CAS  PubMed  Google Scholar 

  72. Brayer, K. J., Lynch, V. J. & Wagner, G. P. Evolution of physical interactions among the transcription factors HoxA-11 and FOXO1a during the evolution of pregnancy in mammals. Soc. Integr. Comp. Biol. 49, E21 (2009).

    Article  CAS  Google Scholar 

  73. Ono, H., Kozmik, Z., Yu, J.-K. & Wada, H. A novel N-terminal motif is responsible for the evolution of neural crest-specific gene-regulatory activity in vertebrate FoxD3. Dev. Biol. 385, 396–404 (2014).

    Article  CAS  PubMed  Google Scholar 

  74. Nitta, K. R. et al. Conservation of transcription factor binding specificities across 600 million years of bilateria evolution. eLife 4, e04837 (2015).

    Article  PubMed Central  Google Scholar 

  75. Kent, M. L. et al. Recent advances in our knowledge of the Myxozoa. J. Eukaryot. Microbiol. 48, 395–413 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Liang, C., FANTOM Consortium, Forrest, A. R. R. & Wagner, G. P. The statistical geometry of transcriptome divergence in cell-type evolution and cancer. Nat. Commun. 6, 6066 (2015).

    Article  CAS  PubMed  Google Scholar 

  77. Owen, R. On the Archetype and Homologies of the Vertebrate Skeleton (John van Voorst, 1848).

    Book  Google Scholar 

  78. Steinmetz, P. R. H. et al. Independent evolution of striated muscles in cnidarians and bilaterians. Nature 487, 231–234 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Stefanakis, N., Carrera, I. & Hobert, O. Regulatory logic of pan-neuronal gene expression in C. elegans. Neuron 87, 733–750 (2015).A systematic investigation of how different neuronal cell types use both cell type-specific and more general regulatory information to express pan-neuronal genes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shalchian-Tabrizi, K. et al. Multigene phylogeny of Choanozoa and the origin of animals. PLoS ONE 3, e2098 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Philippe, H. et al. Phylogenomics revives traditional views on deep animal relationships. Curr. Biol. 19, 706–712 (2009).

    Article  CAS  PubMed  Google Scholar 

  82. Dunn, C. et al. Broad phylogenomic sampling improves resolution of the animal tree of life. Nature 452, 745–749 (2008).

    Article  CAS  PubMed  Google Scholar 

  83. Nickel, M. Evolutionary emergence of synaptic nervous systems: what can we learn from the non-synaptic, nerveless Porifera? Invertebr. Biol. 129, 1–16 (2010).

    Article  Google Scholar 

  84. Jones, W. C. Is there a nervous system in sponges? Biol. Rev. 37, 1–50 (1962).

    Article  CAS  PubMed  Google Scholar 

  85. Simpson, T. L. The Cell Biology of Sponges (Springer Verlag, 1984).

    Book  Google Scholar 

  86. Mackie, G. O. The elementary nervous system revisited. Am. Zool. 30, 907–920 (1990).

    Article  Google Scholar 

  87. Meech, R. W. & Mackie, G. O. in Invertebrate Neurobiology (eds North, G. & Greenspann, J.) 581–615 (Cold Spring Harbor Laboratory Press, 2007).

    Google Scholar 

  88. Leys, S. P. in Porifera Research: Biodiversity, Innovation and Sustainability (eds Custódio, M., Lôbo-Hajdu, G., Hajdu, E. & Muricy, G.) 53–59 (Museu Nacional, 2007).

    Google Scholar 

  89. Smith, C. L. et al. Novel cell types, neurosecretory cells, and body plan of the early-diverging metazoan Trichoplax adhaerens. Curr. Biol. 24, 1565–1572 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Alié, A. & Manuel, M. The backbone of the post-synaptic density originated in a unicellular ancestor of choanoflagellates and metazoans. BMC Evol. Biol. 10, 34 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Sakarya, O. et al. A post-synaptic scaffold at the origin of the animal kingdom. PLoS ONE 2, e506 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Kienle, N., Kloepper, T. H. & Fasshauer, D. Differences in the SNARE evolution of fungi and metazoa. Biochem. Soc. Trans. 37, 787–791 (2009).

    Article  CAS  PubMed  Google Scholar 

  93. Burkhardt, P. et al. Primordial neurosecretory apparatus identified in the choanoflagellate Monosiga brevicollis. Proc. Natl Acad. Sci. USA 108, 15264–15269 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Leys, S. P. & Riesgo, A. Epithelia, an evolutionary novelty of metazoans. J. Exp. Zool. Mol. Dev. Evol. 318, 438–447 (2012).

    Article  Google Scholar 

  95. Grimson, M. J. et al. Adherens junctions and β-catenin-mediated cell signalling in a non-metazoan organism. Nature 408, 727–731 (2000).

    Article  CAS  PubMed  Google Scholar 

  96. Murray, P. S. & Zaidel-Bar, R. Pre-metazoan origins and evolution of the cadherin adhesome. Biol. Open 3, 1183–1195 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Miller, P. W., Clarke, D. N., Weis, W. I., Lowe, C. J. & Nelson, W. J. The evolutionary origin of epithelial cell–cell adhesion mechanisms. Curr. Top. Membr. 72, 267–311 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Bamji, S. X. et al. Role of beta-catenin in synaptic vesicle localization and presynaptic assembly. Neuron 40, 719–731 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Jungling, K. et al. N-Cadherin transsynaptically regulates short-term plasticity at glutamatergic synapses in embryonic stem cell-derived neurons. J. Neurosci. 26, 6968–6978 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Togashi, H. et al. Cadherin regulates dendritic spine morphogenesis. Neuron 35, 77–89 (2002).

    Article  CAS  PubMed  Google Scholar 

  101. Elia, L. P., Yamamoto, M., Zang, K. & Reichardt, L. F. p120 catenin regulates dendritic spine and synapse development through Rho-family GTPases and cadherins. Neuron 51, 43–56 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Bozdagi, O. et al. Persistence of coordinated long-term potentiation and dendritic spine enlargement at mature hippocampal CA1 synapses requires N-cadherin. J. Neurosci. 30, 9984–9989 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Mendez, P., De Roo, M., Poglia, L., Klauser, P. & Muller, D. N-Cadherin mediates plasticity-induced long-term spine stabilization. J. Cell Biol. 189, 589–600 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Conaco, C. et al. Functionalization of a protosynaptic gene expression network. Proc. Natl Acad. Sci. USA 109 (Suppl. 1), 10612–10618 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ori, A. et al. Spatiotemporal variation of mammalian protein complex stoichiometries. Genome Biol. 17, 47 (2016).Provides an expansive look into cell type-specific variation of human protein complexes, suggesting most complexes vary in their composition.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Weimer, C. et al. Differential roles of ArfGAP1, ArfGAP2, and ArfGAP3 in COPI trafficking. J. Cell Biol. 183, 725–735 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kartberg, F. et al. ARFGAP2 and ARFGAP3 are essential for COPI coat assembly on the Golgi membrane of living cells. J. Biol. Chem. 285, 36709–36720 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Emes, R. D. et al. Evolutionary expansion and anatomical specialization of synapse proteome complexity. Nat. Neurosci. 11, 799–806 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Ryan, T. J. & Grant, S. G. N. The origin and evolution of synapses. Nat. Rev. Neurosci. 10, 701–712 (2009).

    Article  CAS  PubMed  Google Scholar 

  110. Emes, R. D. & Grant, S. G. N. Evolution of synapse complexity and diversity. Annu. Rev. Neurosci. 35, 111–131 (2012).

    Article  CAS  PubMed  Google Scholar 

  111. Nithianantharajah, J. et al. Synaptic scaffold evolution generated components of vertebrate cognitive complexity. Nat. Neurosci. 16, 1–11 (2012).

    Google Scholar 

  112. Kin, K. et al. The transcriptomic evolution of mammalian pregnancy: gene expression innovations in endometrial stromal fibroblasts. Genome Biol. Evol. 8, 2459–2473 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Parsons, M. & Adams, J. C. Rac regulates the interaction of fascin with protein kinase C in cell migration. J. Cell Sci. 121, 2805–2813 (2008).

    Article  CAS  PubMed  Google Scholar 

  114. Lin-Jones, J. & Burnside, B. Retina-specific protein fascin 2 is an actin cross-linker associated with actin bundles in photoreceptor inner segments and calycal processes. Invest. Ophthalmol. Vis. Sci. 48, 1380–1388 (2007).

    Article  PubMed  Google Scholar 

  115. Ohno, S. Evolution by Gene Duplication (Springer, 1970).

    Book  Google Scholar 

  116. Lagman, D., Sundström, G., Daza, D. O., Abalo, X. M. & Larhammar, D. Expansion of transducin subunit gene families in early vertebrate tetraploidizations. Genomics 100, 203–211 (2012).

    Article  CAS  PubMed  Google Scholar 

  117. Lagman, D. et al. The vertebrate ancestral repertoire of visual opsins, transducin alpha subunits and oxytocin/vasopressin receptors was established by duplication of their shared genomic region in the two rounds of early vertebrate genome duplications. BMC Evol. Biol. 13, 238 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Fu, Y. & Yau, K.W. Phototransduction in mouse rods and cones. Pflugers Arch. 454, 805–819 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Chen, C. K. et al. Replacing the rod with the cone transducin α subunit decreases sensitivity and accelerates response decay. J. Physiol. (Lond.) 588, 3231–3241 (2010).

    Article  CAS  Google Scholar 

  120. Kawamura, S. & Tachibanaki, S. Rod and cone photoreceptors: molecular basis of the difference in their physiology. Comp. Biochem. Physiol. Physiol. 150, 369–377 (2008).

    Article  CAS  Google Scholar 

  121. Tachibanaki, S., Yonetsu, S. I., Fukaya, S., Koshitani, Y. & Kawamura, S. Low activation and fast inactivation of transducin in carp cones. J. Biol. Chem. 287, 41186–41194 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Korenbrot, J. I. Speed, sensitivity, and stability of the light response in rod and cone photoreceptors: facts and models. Prog. Retin. Eye Res. 31, 442–466 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Reyer, R. W. Regeneration of the lens in the amphibian eye. Q. Rev. Biol. 29, 1–46 (1954).

    Article  CAS  PubMed  Google Scholar 

  124. Sulston, J. E., Schierenberg, E., White, J. G. & Thomson, J. N. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol. 100, 64–119 (1983).

    Article  CAS  PubMed  Google Scholar 

  125. Emerson, M. M., Surzenko, N., Goetz, J. J., Trimarchi, J. & Cepko, C. L. Otx2 and Onecut1 promote the fates of cone photoreceptors and horizontal cells and repress rod photoreceptors. Dev. Cell 26, 59–72 (2013).

    Article  CAS  PubMed  Google Scholar 

  126. Bayraktar, O. A. & Doe, C. Q. Combinatorial temporal patterning in progenitors expands neural diversity. Nature 498, 449–455 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Sternberg, P. W. & Horvitz, H. R. The genetic control of cell lineage during nematode development. Annu. Rev. Genet. 18, 489–524 (1984).

    Article  CAS  PubMed  Google Scholar 

  128. Fritzsch, B., Beisel, K. W., Pauley, S. & Soukup, G. Molecular evolution of the vertebrate mechanosensory cell and ear. Int. J. Dev. Biol. 51, 663–678 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Fritzsch, B. & Piatigorsky, J. Ancestry of photic and mechanic sensation? Science 308, 1113–1114 (2005).

    Article  CAS  PubMed  Google Scholar 

  130. Fritzsch, B., Beisel, K. W. & Bermingham, N. A. Developmental evolutionary biology of the vertebrate ear: conserving mechanoelectric transduction and developmental pathways in diverging morphologies. Neuroreport 11, R35–R44 (2000).

    Article  CAS  PubMed  Google Scholar 

  131. Wang, Z., Young, R. L., Xue, H. & Wagner, G. P. Transcriptomic analysis of avian digits reveals conserved and derived digit identities in birds. Nature 477, 583–586 (2011).

    Article  CAS  PubMed  Google Scholar 

  132. Nair, N. U. et al. A maximum-likelihood approach for building cell-type trees by lifting. BMC Genomics 17 (Suppl. 1), 14 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  133. Pavlicev, M. & Widder, S. Wiring for independence: positive feedback motifs facilitate individuation of traits in development and evolution. J. Exp. Zool. 324, 104–113 (2015).

    Article  Google Scholar 

  134. Dueck, H. et al. Deep sequencing reveals cell-type-specific patterns of single-cell transcriptome variation. Genome Biol. 16, 122 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. Dueck, H., Eberwine, J. & Kim, J. Variation is function: are single cell differences functionally important? Testing the hypothesis that single cell variation is required for aggregate function. Bioessays 38, 172–180 (2016).

    Article  PubMed  Google Scholar 

  136. Brunskill, E. W. et al. Single cell dissection of early kidney development: multilineage priming. Development 141, 3093–3101 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. McKenna, A. et al. Whole organism lineage tracing by combinatorial and cumulative genome editing. Science 353, aaf7907 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Wang, S., Sengel, C., Emerson, M. M. & Cepko, C. L. A gene regulatory network controls the binary fate decision of rod and bipolar cells in the vertebrate retina. Dev. Cell 30, 513–527 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Corbo, J. C., Myers, C. A., Lawrence, K. A., Jadhav, A. P. & Cepko, C. L. A typology of photoreceptor gene expression patterns in the mouse. Proc. Natl Acad. Sci. USA 104, 12069–12074 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Kim, D. S. et al. Identification of molecular markers of bipolar cells in the murine retina. J. Comp. Neurol. 507, 1795–1810 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Arendt, D., Tessmar-Raible, K., Snyman, H., Dorresteijn, A. W. & Wittbrodt, J. Ciliary photoreceptors with a vertebrate-type opsin in an invertebrate brain. Science 306, 869–871 (2004).

    Article  CAS  PubMed  Google Scholar 

  142. Cepko, C. Intrinsically different retinal progenitor cells produce specific types of progeny. Nat. Rev. Neurosci. 15, 615–627 (2014).

    Article  CAS  PubMed  Google Scholar 

  143. Centanin, L. et al. Exclusive multipotency and preferential asymmetric divisions in post-embryonic neural stem cells of the fish retina. Development 141, 3472–3482 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Fujiyama, T. et al. Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1. Development 136, 2049–2058 (2009).

    Article  CAS  PubMed  Google Scholar 

  145. Yamada, M. et al. Specification of spatial identities of cerebellar neuron progenitors by ptf1a and atoh1 for proper production of GABAergic and glutamatergic neurons. J. Neurosci. 34, 4786–4800 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Tosches, M. A. & Arendt, D. The bilaterian forebrain: an evolutionary chimaera. Curr. Opin. Neurobiol. 23, 1080–1089 (2013).

    Article  CAS  PubMed  Google Scholar 

  147. Xiang, M. et al. Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development. Proc. Natl Acad. Sci. USA 94, 9445–9450 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Bermingham, N. A. et al. Math1: an essential gene for the generation of inner ear hair cells. Science 284, 1837–1841 (1999).

    Article  CAS  PubMed  Google Scholar 

  149. Wallis, D. et al. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development 130, 221–232 (2003).

    Article  CAS  PubMed  Google Scholar 

  150. Eijkelkamp, N., Quick, K. & Wood, J. N. Transient receptor potential channels and mechanosensation. Annu. Rev. Neurosci. 36, 519–546 (2013).

    Article  CAS  PubMed  Google Scholar 

  151. Schlosser, G. Vertebrate cranial placodes as evolutionary innovations — the ancestor's tale. Curr. Top. Dev. Biol. 111, 235–300 (2015).Reconstructs the evolutionary history of neurogenic placodes in vertebrates, and based on evolutionary and developmental evidence suggests a hierarchy of relatedness among different placode-derived organs.

    Article  CAS  PubMed  Google Scholar 

  152. Arendt, D., Benito-Gutierrez, E., Brunet, T. & Marlow, H. Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution. Philos. Trans. R. Soc. B 370, 20150286 (2015).

    Article  CAS  Google Scholar 

  153. Satoh, T. & Fekete, D. M. Clonal analysis of the relationships between mechanosensory cells and the neurons that innervate them in the chicken ear. Development 132, 1687–1697 (2005).

    Article  CAS  PubMed  Google Scholar 

  154. Simionato, E. et al. atonal- and achaete-scute-related genes in the annelid Platynereis dumerilii: insights into the evolution of neural basic-helix–loop–helix genes. BMC Evol. Biol. 8, 170 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  155. Baker, C. V. H., Modrell, M. S. & Gillis, J. A. The evolution and development of vertebrate lateral line electroreceptors. J. Exp. Biol. 216, 2515–2522 (2013).

    Article  PubMed  Google Scholar 

  156. Whitear, M. Merkel cells in lower vertebrates. Arch. Histol. Cytol. 52 (Suppl.), 415–422 (1989).

    Article  PubMed  Google Scholar 

  157. Woo, S.-H., Lumpkin, E. A. & Patapoutian, A. Merkel cells and neurons keep in touch. Trends Cell Biol. 25, 74–81 (2015).

    Article  PubMed  Google Scholar 

  158. Masuda, M. et al. Regulation of POU4F3 gene expression in hair cells by 5′ DNA in mice. Neuroscience 197, 48–64 (2011).

    Article  CAS  PubMed  Google Scholar 

  159. Tang, J. W., Chen, J. S. & Zeller, R. W. Transcriptional regulation of the peripheral nervous system in Ciona intestinalis. Dev. Biol. 378, 183–193 (2013).

    Article  CAS  Google Scholar 

  160. Stolfi, A., Ryan, K., Meinertzhagen, I. A. & Christiaen, L. Migratory neuronal progenitors arise from the neural plate borders in tunicates. Nature 527, 371–374 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Eisenhoffer, G. T. & Rosenblatt, J. Bringing balance by force: live cell extrusion controls epithelial cell numbers. Trends Cell Biol. 23, 185–192 (2013).

    Article  CAS  PubMed  Google Scholar 

  162. Cowdry, E. V. General Cytology: A Textbook of Cellular Structure and Function for Students of Biology and Medicine (The Univ. of Chicago Press, 1924).

    Book  Google Scholar 

  163. Wilson, E. B. The Cell in Development and Heredity (The Macmillan Company, 1925).

    Google Scholar 

  164. Harris, H. The Cells of the Body: A History of Somatic Cell Genetics (Cold Spring Harbor Laboratory Press, 1995).

    Google Scholar 

  165. Harris, H. The Birth of the Cell (Yale Univ. Press, 1999).

    Google Scholar 

  166. Hertwig, O. Handbuch der Vergleichenden und Experimentellen Entwickelungslehre der Wirbeltiere (in German) (Fischer, 1906).

    Google Scholar 

  167. Strasburger, E. & Hertwig, O. Zellen- und Gewebelehre, Morphologie, und Entwicklungsgeschichte (in German) (B. G. Teubner, 1913).

    Google Scholar 

  168. Maienschein, J. Transforming Traditions in American Biology, 1880–1915 (Johns Hopkins Univ. Press, 1991).

    Google Scholar 

  169. Morgan, T. H. The Mechanism of Mendelian Heredity (Holt, 1915).

    Google Scholar 

  170. Boveri, T. Die Organismen als Historische Wesen (in German) (Kgl. Universitätsdruckerei von H. Stürtz, 1906).An early conceptual account that introduces the idea that developmental differentiation and evolutionary differentiation must be a consequence of regulatory structures within the hereditary material.

    Google Scholar 

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Acknowledgements

This paper resulted from discussions of a working group at the Santa Fe Institute (SFI), New Mexico, USA, sponsored by the Arizona State University (ASU)-SFI Center for Biosocial Complex Systems. The authors are grateful for their support. Research on neuron type evolution in the Arendt laboratory is financially supported by a European Research Council Advanced grant (294810 Brain Evo-Devo). Research on cell type origination in the Wagner laboratory is financially supported by a grant from the John Templeton Foundation (grant no. 54860). The opinions expressed in this article are not those of the John Templeton Foundation.

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Author notes

  1. Detlev Arendt and Jacob M. Musser: These authors contributed equally to this work.

Authors and Affiliations

  1. Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, 69012, Germany

    Detlev Arendt & Jacob M. Musser

  2. Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, Heidelberg, 69120, Germany

    Detlev Arendt

  3. Department of Physiology, Development and Neuroscience, University of Cambridge, Anatomy Building, Downing Street, Cambridge, CB2 3DY, UK

    Clare V. H. Baker

  4. Department of Systems and Computational Biology, Dominick P. Purpura Department of Neuroscience, and Department of Pathology, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, 10461, New York, USA

    Aviv Bergman

  5. Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, 87501, New Mexico, USA

    Aviv Bergman, Douglas H. Erwin & Manfred D. Laubichler

  6. Department of Genetics and Department of Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Connie Cepko

  7. Department of Paleobiology, MRC-121, Smithsonian Institution, PO Box 37012, 20013–7012, Washington, DC, USA

    Douglas H. Erwin

  8. Cincinnati Children's Hospital Medical Center, Perinatal Institute, Cincinnati, 45229–3026, Ohio, USA

    Mihaela Pavlicev

  9. School of Natural Science and Regenerative Medicine Institute (REMEDI), Biomedical Science Building, Newcastle Road, Galway, Ireland

    Gerhard Schlosser

  10. Department of Microbial Ecology and Ecosystem Sciences, CUBE, University of Vienna, Althanstrasse 14, Vienna, 1090, Austria

    Stefanie Widder

  11. School of Life Sciences, Arizona State University, PO Box 4501, Tempe, 85287–4501, Arizona, USA

    Manfred D. Laubichler

  12. Marine Biological Laboratory, 7 MBL Street, Woods Hole, 02543, Massachusetts, USA

    Manfred D. Laubichler

  13. Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, 06511, Connecticut, USA

    Günter P. Wagner

  14. Department of Obstetrics, Gynecology and Reproductive Science, Yale University Medical School, New Haven, 06510, Connecticut, USA

    Günter P. Wagner

  15. Department of Obstetrics and Gynecology, Wayne State University, Detroit, 48201, Michigan, USA

    Günter P. Wagner

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  1. Detlev Arendt
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Correspondence to Detlev Arendt, Manfred D. Laubichler or Günter P. Wagner.

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PowerPoint slides

Glossary

Cellular modules

Protein complexes, pathways and molecular machines that make up cell structure and function.

Cell type homology

Cell types that trace back to the same cell type in a common ancestor.

Cell phenotypic convergence

Cell types that are phenotypically similar due to independent changes occurring in separate evolutionary lineages.

Concerted evolution

Similar phenotypic changes that occur simultaneously across different cell types of the same species as a result of altering genetic information shared among the cell types.

Sister cell types

Cell types arising by the splitting of an ancestral cell type into two descendant cells via the process of individuation.

Evolutionary units

Modular biological entities capable of evolving as a cohesive unit and at least partially independently of others (for example, genes, cell types and species).

Genetic individuation

The evolutionary independence of cell types resulting from the differential use of genomic information.

Core regulatory complex

(CoRC). A protein complex composed of terminal selector transcription factors that enables and maintains the distinct gene expression programme of a cell.

Terminal selectors

A set of transcription factors that directly regulates the cell type-specific set of effector genes and represses alternative cell type identities.

Apomeres

Derived cell type-specific cellular modules.

Synapomeres

Ancestral apomeres now shared by descendant sister cell types.

Pan-neuronal genes

Genes expressed broadly, but not exclusively, in neurons; for example, synaptic and vesicular genes.

Module integration

Evolution of a new functional complex or pathway by colocalization and integration of pre-existing functional machinery.

Module divergence

Evolution of cell type-specific variation in protein complexes or pathways; commonly occurs by gene duplication and divergence.

SNARE

Soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein (SNAP) receptor.

Cell type fusion

Co-option of a second core regulatory complex into an existing cell type, creating a cell type hybrid of two different ancestral cell type identities.

Serial sister cell types

Sister cell types that arise from different developmental lineages or regions of the body.

Sensory placodes

Thickened patches of embryonic head ectoderm that contribute sensory receptor cells, secretory cells and supporting cells to peripheral sense organs, and/or sensory neurons to cranial ganglia.

Comparative connectomics

A research programme comparing the neuronal connection networks between species.

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Arendt, D., Musser, J., Baker, C. et al. The origin and evolution of cell types. Nat Rev Genet 17, 744–757 (2016). https://doi.org/10.1038/nrg.2016.127

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