Article | Published:

Transcriptional landscape of the prenatal human brain

Nature volume 508, pages 199206 (10 April 2014) | Download Citation

Abstract

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    et al. Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature 478, 519–523 (2011)

  2. 2.

    et al. Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal. Proc. Natl Acad. Sci. USA 109, 11836–11841 (2012)

  3. 3.

    et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 62, 494–509 (2009)

  4. 4.

    et al. Spatio-temporal transcriptome of the human brain. Nature 478, 483–489 (2011)

  5. 5.

    et al. Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution. PLoS ONE 6, e17753 (2011)

  6. 6.

    , & Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nature Rev. Neurosci. 7, 883–890 (2006)

  7. 7.

    , , & Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464, 554–561 (2010)

  8. 8.

    , , , & Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cereb.Cortex 12, 37–53 (2002)

  9. 9.

    The subpial granular layer of the foetal cerebral cortex in man. Its ontogeny and significance in congenital cortical malformations. Acta Pathologica et Microbiologica Scandinavica 179 (suppl.). 3–98 (1965)

  10. 10.

    , , & Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278, 474–476 (1997)

  11. 11.

    et al. Subcortical origins of human and monkey neocortical interneurons. Nature Neurosci. 16, 1588–1597 (2013)

  12. 12.

    & Dorsal radial glial cells have the potential to generate cortical interneurons in human but not in mouse brain. J. Neurosci. 31, 2413–2420 (2011)

  13. 13.

    , & Origin of GABAergic neurons in the human neocortex. Nature 417, 645–649 (2002)

  14. 14.

    et al. Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences. Nature Neurosci. 16, 1576–1587 (2013)

  15. 15.

    , , & Accelerated evolution of conserved noncoding sequences in humans. Science 314, 786 (2006)

  16. 16.

    et al. Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing. Proc. Natl Acad. Sci. USA 108, 14950–14955 (2011)

  17. 17.

    et al. Hypothesis on the dual origin of the mammalian subplate. Front. Neuroanat. 5, 25 (2011)

  18. 18.

    et al. Comparative aspects of subplate zone studied with gene expression in sauropsids and mammals. Cereb. Cortex 21, 2187–2203 (2011)

  19. 19.

    Rethinking schizophrenia. Nature 468, 187–193 (2010)

  20. 20.

    & Paxinos and Franklin’s the Mouse Brain in Stereotaxic Coordinates 4th edn (Academic Press, 2012)

  21. 21.

    & A Combined MRI and Histology Atlas of the Rhesus Monkey Brain in Stereotaxic Coordinates 2nd edition (Academic Press, 2012)

  22. 22.

    Allen Reference Atlas: a Digital Color Brain Atlas of the C57BL/6J Male Mouse (Wiley, 2008)

  23. 23.

    et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391–399 (2012)

  24. 24.

    et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176 (2007)

  25. 25.

    et al. Transcriptional architecture of the primate neocortex. Neuron 73, 1083–1099 (2012)

  26. 26.

    et al. Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism. Am. J. Hum. Genet. 85, 354–363 (2009)

  27. 27.

    et al. Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype–phenotype correlations. Hum. Mutat. 24, 43–51 (2004)

  28. 28.

    et al. Anatomical characterization of human fetal brain development with diffusion tensor magnetic resonance imaging. J. Neurosci. 29, 4263–4273 (2009)

  29. 29.

    , & Development of the human cerebral cortex: Boulder Committee revisited. Nature Rev. Neurosci. 9, 110–122 (2008)

  30. 30.

    , & Localization of calretinin in cells of layer I (Cajal-Retzius cells) of the developing cortex of the rat. Brain Res. Dev. Brain Res. 82, 293–297 (1994)

  31. 31.

    et al. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J. Neurosci. 25, 247–251 (2005)

  32. 32.

    & Immunoperoxidase localization of glial fibrillary acidic protein in radial glial cells and astrocytes of the developing rhesus monkey brain. J. Comp. Neurol. 193, 815–840 (1980)

  33. 33.

    et al. Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation. Nature Genet. 36, 1053–1055 (2004)

  34. 34.

    , , & Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly. J. Neurosci. 28, 4712–4725 (2008)

  35. 35.

    & The development of the subplate and thalamocortical connections in the human foetal brain. Acta Paediatr. 99, 1119–1127 (2010)

  36. 36.

    & A general framework for weighted gene co-expression network analysis. Stat. Appl. Genet. Mol. Biol. 4, 17 (2005)

  37. 37.

    et al. Functional organization of the transcriptome in human brain. Nature Neurosci. 11, 1271–1282 (2008)

  38. 38.

    et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474, 380–384 (2011)

  39. 39.

    et al. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell 155, 1008–1021 (2013)

  40. 40.

    et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell 155, 997–1007 (2013)

  41. 41.

    & Laminar fate specification in the cerebral cortex. F1000 Biol. Rep. 3, 6 (2011)

  42. 42.

    et al. Precursor diversity and complexity of lineage relationships in the outer subventricular zone of the primate. Neuron 80, 442–457 (2013)

  43. 43.

    et al. Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis. Development 135, 3113–3124 (2008)

  44. 44.

    , , , & Mouse brain potassium channel β1 subunit mRNA: cloning and distribution during development. J. Neurobiol. 34, 135–150 (1998)

  45. 45.

    et al. Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. J. Neurosci. 21, 7273–7283 (2001)

  46. 46.

    & Gene networks controlling early cerebral cortex arealization. Eur. J. Neurosci. 23, 847–856 (2006)

  47. 47.

    Do cortical areas emerge from a protocortex? Trends Neurosci. 12, 400–406 (1989)

  48. 48.

    Specification of cerebral cortical areas. Science 241, 170–176 (1988)

  49. 49.

    & Gradients in the brain: the control of the development of form and function in the cerebral cortex. Cold Spring Harb. Perspect. Biol. 1, a002519 (2009)

  50. 50.

    The cerebral cortex malformation in thanatophoric dysplasia: neuropathology and pathogenesis. Acta Neuropathol. 110, 208–221 (2005)

  51. 51.

    et al. AP2γ regulates basal progenitor fate in a region- and layer-specific manner in the developing cortex. Nature Neurosci. 12, 1229–1237 (2009)

  52. 52.

    Neurogenesis in adult primates. Prog. Brain Res. 138, 3–14 (2002)

  53. 53.

    & The subplate, a transient neocortical structure: its role in the development of connections between thalamus and cortex. Annu. Rev. Neurosci. 17, 185–218 (1994)

  54. 54.

    et al. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869–872 (2002)

  55. 55.

    et al. Single-neuron RNA-seq: technical feasibility and reproducibility. Front. Genet. 3, 124 (2012)

  56. 56.

    et al. Correlated gene expression and target specificity demonstrate excitatory projection neuron diversity. Cereb. Cortex (2013)

  57. 57.

    , & Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8, 118–127 (2007)

  58. 58.

    & WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9, 559 (2008)

  59. 59.

    & Eigengene networks for studying the relationships between co-expression modules. BMC Syst. Biol. 1, 54 (2007)

  60. 60.

    , & Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols 4, 44–57 (2009)

  61. 61.

    et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264–278 (2008)

  62. 62.

    et al. Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nature Neurosci. 9, 99–107 (2006)

  63. 63.

    et al. Strategies for aggregating gene expression data: the collapseRows R function. BMC Bioinformatics 12, 322 (2011)

  64. 64.

    , , & VisANT: an online visualization and analysis tool for biological interaction data. BMC Bioinformatics 5, 17 (2004)

Download references

Acknowledgements

We wish to thank the Allen Institute founders, P. G. Allen and J. Allen, for their vision, encouragement and support. We express our gratitude to past and present Allen Institute staff members R. Adams, A. Alpisa, A. Boe, E. Byrnes, M. Chapin, J. Chen, C. Copeland, N. Dotson, K. Fotheringham, E. Fulfs, M. Gasparrini, T. Gilbert, Z. Haradon, N. Hejazinia, N. Ivanov, J. Kinnunen, A. Kriedberg, J. Laoenkue, S. Levine, V. Menon, E. Mott, N. Motz, J. Pendergraft, L. Potekhina, J. Redmayne-Titley, D. Rosen, C. Simpson, S. Shi, L. Velasquez, U. Wagley, N. Wong and B. Youngstrom for their technical assistance. We would also like to thank J. Augustinack, T. Benner, A. Mayaram, M. Roy, A. van der Kouwe and L. Wald from the Fischl laboratory. Also, we wish to acknowledge Covance Genomics Laboratory (Seattle, Washington) for microarray probe generation, hybridization and scanning. In addition, we express our gratitude to Advanced Bioscience Resources, for providing tissue used for expression profiling and reference atlas generation as well as to the Laboratory of Developmental Biology, University of Washington, for providing tissue used for expression profiling and reference atlas generation. The Laboratory of Developmental Biology work was supported by the National Institutes of Health (NIH) Award Number 5R24HD0008836 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The BrainSpan project was supported by Award Number RC2MH089921 (PIs: E. Lein and M. Hawrylycz, Allen Institute for Brain Science) from the National Institute of Mental Health. The content is solely the responsibility of the respective authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health.

Author information

Author notes

    • Jeremy A. Miller
    •  & Song-Lin Ding

    These authors contributed equally to this work.

Affiliations

  1. Allen Institute for Brain Science, Seattle, Washington 98103, USA

    • Jeremy A. Miller
    • , Song-Lin Ding
    • , Susan M. Sunkin
    • , Kimberly A. Smith
    • , Lydia Ng
    • , Aaron Szafer
    • , Amanda Ebbert
    • , Zackery L. Riley
    • , Joshua J. Royall
    • , Kaylynn Aiona
    • , James M. Arnold
    • , Crissa Bennet
    • , Darren Bertagnolli
    • , Krissy Brouner
    • , Stephanie Butler
    • , Shiella Caldejon
    • , Anita Carey
    • , Christine Cuhaciyan
    • , Rachel A. Dalley
    • , Nick Dee
    • , Tim A. Dolbeare
    • , Benjamin A. C. Facer
    • , David Feng
    • , Tim P. Fliss
    • , Garrett Gee
    • , Jeff Goldy
    • , Lindsey Gourley
    • , Benjamin W. Gregor
    • , Guangyu Gu
    • , Robert E. Howard
    • , Jayson M. Jochim
    • , Chihchau L. Kuan
    • , Christopher Lau
    • , Chang-Kyu Lee
    • , Felix Lee
    • , Tracy A. Lemon
    • , Phil Lesnar
    • , Bergen McMurray
    • , Naveed Mastan
    • , Nerick Mosqueda
    • , Nhan-Kiet Ngo
    • , Julie Nyhus
    • , Aaron Oldre
    • , Eric Olson
    • , Jody Parente
    • , Patrick D. Parker
    • , Sheana E. Parry
    • , Melissa Reding
    • , Kate Roll
    • , David Sandman
    • , Melaine Sarreal
    • , Sheila Shapouri
    • , Nadiya V. Shapovalova
    • , Elaine H. Shen
    • , Nathan Sjoquist
    • , Clifford R. Slaughterbeck
    • , Michael Smith
    • , Andy J. Sodt
    • , Derric Williams
    • , Michael J. Hawrylycz
    • , Allan R. Jones
    • , John W. Phillips
    • , Paul Wohnoutka
    • , Chinh Dang
    • , Amy Bernard
    • , John G. Hohmann
    •  & Ed S. Lein
  2. Division of Genetic Medicine, Department of Pediatrics, University of Washington, 1959 North East Pacific Street, Box 356320, Seattle, Washington 98195, USA

    • Theresa Naluai-Cecchini
    •  & Ian A. Glass
  3. Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA

    • Allison Stevens
    • , Lilla Zöllei
    •  & Bruce Fischl
  4. Computer Science and AI Lab, MIT, Cambridge, Massachusetts 02139, USA

    • Allison Stevens
    •  & Bruce Fischl
  5. Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA

    • Mihovil Pletikos
    •  & Nenad Šestan
  6. Program in Computational Biology and Bioinformatics, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA

    • Mark B. Gerstein
  7. Department of Computer Science, Yale University, New Haven, Connecticut 06520, USA

    • Mark B. Gerstein
  8. Program in Neurogenetics, Department of Neurology and Semel Institute David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA

    • Daniel H. Geschwind
  9. Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, Washington 98101, USA

    • Robert F. Hevner
  10. Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington 98105, USA

    • Robert F. Hevner
  11. Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas 75390, USA

    • Hao Huang
  12. Zilkha Neurogenetic Institute, and Department of Psychiatry, University of Southern California, Los Angeles, California 90033, USA

    • James A. Knowles
  13. Department of Pediatrics, Children’s Hospital, Los Angeles, California 90027, USA

    • Pat Levitt
  14. Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA

    • Pat Levitt

Authors

  1. Search for Jeremy A. Miller in:

  2. Search for Song-Lin Ding in:

  3. Search for Susan M. Sunkin in:

  4. Search for Kimberly A. Smith in:

  5. Search for Lydia Ng in:

  6. Search for Aaron Szafer in:

  7. Search for Amanda Ebbert in:

  8. Search for Zackery L. Riley in:

  9. Search for Joshua J. Royall in:

  10. Search for Kaylynn Aiona in:

  11. Search for James M. Arnold in:

  12. Search for Crissa Bennet in:

  13. Search for Darren Bertagnolli in:

  14. Search for Krissy Brouner in:

  15. Search for Stephanie Butler in:

  16. Search for Shiella Caldejon in:

  17. Search for Anita Carey in:

  18. Search for Christine Cuhaciyan in:

  19. Search for Rachel A. Dalley in:

  20. Search for Nick Dee in:

  21. Search for Tim A. Dolbeare in:

  22. Search for Benjamin A. C. Facer in:

  23. Search for David Feng in:

  24. Search for Tim P. Fliss in:

  25. Search for Garrett Gee in:

  26. Search for Jeff Goldy in:

  27. Search for Lindsey Gourley in:

  28. Search for Benjamin W. Gregor in:

  29. Search for Guangyu Gu in:

  30. Search for Robert E. Howard in:

  31. Search for Jayson M. Jochim in:

  32. Search for Chihchau L. Kuan in:

  33. Search for Christopher Lau in:

  34. Search for Chang-Kyu Lee in:

  35. Search for Felix Lee in:

  36. Search for Tracy A. Lemon in:

  37. Search for Phil Lesnar in:

  38. Search for Bergen McMurray in:

  39. Search for Naveed Mastan in:

  40. Search for Nerick Mosqueda in:

  41. Search for Theresa Naluai-Cecchini in:

  42. Search for Nhan-Kiet Ngo in:

  43. Search for Julie Nyhus in:

  44. Search for Aaron Oldre in:

  45. Search for Eric Olson in:

  46. Search for Jody Parente in:

  47. Search for Patrick D. Parker in:

  48. Search for Sheana E. Parry in:

  49. Search for Allison Stevens in:

  50. Search for Mihovil Pletikos in:

  51. Search for Melissa Reding in:

  52. Search for Kate Roll in:

  53. Search for David Sandman in:

  54. Search for Melaine Sarreal in:

  55. Search for Sheila Shapouri in:

  56. Search for Nadiya V. Shapovalova in:

  57. Search for Elaine H. Shen in:

  58. Search for Nathan Sjoquist in:

  59. Search for Clifford R. Slaughterbeck in:

  60. Search for Michael Smith in:

  61. Search for Andy J. Sodt in:

  62. Search for Derric Williams in:

  63. Search for Lilla Zöllei in:

  64. Search for Bruce Fischl in:

  65. Search for Mark B. Gerstein in:

  66. Search for Daniel H. Geschwind in:

  67. Search for Ian A. Glass in:

  68. Search for Michael J. Hawrylycz in:

  69. Search for Robert F. Hevner in:

  70. Search for Hao Huang in:

  71. Search for Allan R. Jones in:

  72. Search for James A. Knowles in:

  73. Search for Pat Levitt in:

  74. Search for John W. Phillips in:

  75. Search for Nenad Šestan in:

  76. Search for Paul Wohnoutka in:

  77. Search for Chinh Dang in:

  78. Search for Amy Bernard in:

  79. Search for John G. Hohmann in:

  80. Search for Ed S. Lein in:

Contributions

E.S.L, S.-L.D., K.A.S. and S.M.S. contributed significantly to the overall project design. S.M.S, K.A.S., A.E., A.B., and P.W. managed the tissue and sample processing in the laboratory. K.A., J.M.A., C.B., D.B., K.B., S.B., S.C., A.C., C.C., R.A.D., G.Ge., J.G., L.G., B.W.G., R.E.H., T.A.L., Na.M., N.F.M., N.-K.N., A.O., E.O., J.Pa., P.D.P., S.E.P., M.P., Me.R., J.J.R., K.R., D.S., Me.S., S.S., N.V.S. and Mi.S. contributed to tissue and sample processing. E.H.S., Z.L.R., T.N.-C., and I.A.G. contributed to establishing the tissue acquisition pipeline. N.D., J.N. and A.B. contributed to protocol development. A.S.P., L.Z., B.F., and H.H. contributed to MR and DWI imaging and analysis. J.M.J., C.R.S., and D.W. provided engineering support. S.-L.D., R.A.D., P.D.P., D.S. and J.G.H. contributed to the neuroanatomical design and implementation. S.-L.D., B.A.C.F., Ph.L., B.M., J.J.R., R.F.H., N.Se. and J.G.H. contributed to the reference atlas design, quality control and implementation. L.N., A.S. and C.D. managed the creation of the data pipeline, visualization and mining tools. L.N., A.S., T.A.D., D.F., T.P.F., G.Gu, C.L.K., C.La., F.L., N.Sj. and A.J.S. contributed to the creation of the data pipeline, visualization and mining tools. J.A.M., S.-L.D., R.F.H., C.-K.L., M.J.H., S.M.S. and E.S.L. contributed to data analysis and interpretation. M.B.G., D.H.G., J.A.K., Pa.L., J.W.P., N.Se. and A.R.J. contributed to overall project design and consortium management. E.S.L. and M.J.H. conceived the project, and the manuscript was written by J.A.M. and E.S.L. with input from all other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ed S. Lein.

These data are freely accessible as part of the BrainSpan Atlas of the Developing Human Brain (http://brainspan.org), also available via the Allen Brain Atlas data portal (http://www.brain-map.org).

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Methods and Supplementary Table 1, which gives additional biological insights into the prenatal human brain.

Excel files

  1. 1.

    Supplementary Table 2

    Complete ontology for the BrainSpan project, showing the subset of structures and layers assayed in this study. Further details in the "Key" tab of the spreadsheet.

  2. 2.

    Supplementary Table 3 and 4

    Layer of maximal expression (with statistics) for each gene in each brain (Supplementary Table 3). These data were used for Figure 2d. Enrichment analysis for laminar genes at 21pcw (Supplementary Table 4). Significantly enriched gene ontology and brain-related categories are listed. Further details in the "Key" tab of the spreadsheet.

  3. 3.

    Supplementary Table 5

    Module assignments and module membership for each gene in the cortical network. Genes listed in Figure 3b were chosen from this table. Further details in the "Key" tab of the spreadsheet.

  4. 4.

    Supplementary Table 6

    Enrichment analysis for genes in each cortical network module. Significantly enriched DAVID categories and relevant brain-related categories, including cell type enrichment are listed. Details are described in the worksheet labeled "Key".

  5. 5.

    Supplementary Table 7

    Enrichment analysis for genes in each germinal network module. Significantly enriched DAVID categories and relevant brain-related categories, including cell type enrichment are listed. Details are described in the worksheet labeled "Key".

  6. 6.

    Supplementary Table 8

    150 marker genes for human and/or mouse subplate, along with evidence for defining these genes as SP markers. Genes listed in Figure 4 were selected from this table. Further details in the "Key" tab of the spreadsheet.

  7. 7.

    Supplementary Table 9

    All genes identified as showing frontal to temporal gradient patterning in the developing human neocortex are included. Subsets of these genes, which are associated with human accelerated conserved noncoding sequences (haCNSs) or that are consistent with mouse, are also highlighted. Further details in the "Key" tab of the spreadsheet.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nature13185

Further reading

  • Analysis of the expression pattern of the schizophrenia-risk and intellectual disability gene TCF4 in the developing and adult brain suggests a role in development and plasticity of cortical and hippocampal neurons

    • Matthias Jung
    • , Benjamin M. Häberle
    • , Tristan Tschaikowsky
    • , Marie-Theres Wittmann
    • , Elli-Anna Balta
    • , Vivien-Charlott Stadler
    • , Christiane Zweier
    • , Arnd Dörfler
    • , Christian Johannes Gloeckner
    •  & D. Chichung Lie

    Molecular Autism (2018)

  • Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type

    • Eszter Boldog
    • , Trygve E. Bakken
    • , Rebecca D. Hodge
    • , Mark Novotny
    • , Brian D. Aevermann
    • , Judith Baka
    • , Sándor Bordé
    • , Jennie L. Close
    • , Francisco Diez-Fuertes
    • , Song-Lin Ding
    • , Nóra Faragó
    • , Ágnes K. Kocsis
    • , Balázs Kovács
    • , Zoe Maltzer
    • , Jamison M. McCorrison
    • , Jeremy A. Miller
    • , Gábor Molnár
    • , Gáspár Oláh
    • , Attila Ozsvár
    • , Márton Rózsa
    • , Soraya I. Shehata
    • , Kimberly A. Smith
    • , Susan M. Sunkin
    • , Danny N. Tran
    • , Pratap Venepally
    • , Abby Wall
    • , László G. Puskás
    • , Pál Barzó
    • , Frank J. Steemers
    • , Nicholas J. Schork
    • , Richard H. Scheuermann
    • , Roger S. Lasken
    • , Ed S. Lein
    •  & Gábor Tamás

    Nature Neuroscience (2018)

  • Ptchd1 deficiency induces excitatory synaptic and cognitive dysfunctions in mouse

    • D C Ung
    • , G Iacono
    • , H Méziane
    • , E Blanchard
    • , M-A Papon
    • , M Selten
    • , J-R van Rhijn
    • , R Montjean
    • , J Rucci
    • , S Martin
    • , A Fleet
    • , M-C Birling
    • , S Marouillat
    • , R Roepman
    • , M Selloum
    • , A Lux
    • , R-A Thépault
    • , P Hamel
    • , K Mittal
    • , J B Vincent
    • , O Dorseuil
    • , H G Stunnenberg
    • , P Billuart
    • , N Nadif Kasri
    • , Y Hérault
    •  & F Laumonnier

    Molecular Psychiatry (2018)

  • Investigating the neuroimmunogenic architecture of schizophrenia

    • R Birnbaum
    • , A E Jaffe
    • , Q Chen
    • , J H Shin
    • , Christian R Schubert
    • , Patricio O'Donnell
    • , Jie Quan
    • , Jens R Wendland
    • , Hualin S Xi
    • , Ashley R Winslow
    • , Enrico Domenici
    • , Laurent Essioux
    • , Tony Kam-Thong
    • , David C Airey
    • , John N Calley
    • , David A Collier
    • , Hong Wang
    • , Brian Eastwood
    • , Philip Ebert
    • , Yushi Liu
    • , Laura Nisenbaum
    • , Cara Ruble
    • , James Scherschel
    • , Ryan Matthew Smith
    • , Hui-Rong Qian
    • , Kalpana Merchant
    • , Michael Didriksen
    • , Mitsuyuki Matsumoto
    • , Takeshi Saito
    • , Nicholas J Brandon
    • , Alan J Cross
    • , Qi Wang
    • , Husseini Manji
    • , Hartmuth Kolb
    • , Maura Furey
    • , Wayne C Drevets
    • , Joo Heon Shin
    • , Andrew E Jaffe
    • , Yankai Jia
    • , Richard E Straub
    • , Amy Deep-Soboslay
    • , Thomas M Hyde
    • , Joel E Kleinman
    • , Daniel R Weinberger
    • , J E Kleinman
    • , T M Hyde
    •  & D R Weinberger

    Molecular Psychiatry (2018)

  • Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence

    • Sevin Turcan
    • , Vladimir Makarov
    • , Julian Taranda
    • , Yuxiang Wang
    • , Armida W. M. Fabius
    • , Wei Wu
    • , Yupeng Zheng
    • , Nour El-Amine
    • , Sara Haddock
    • , Gouri Nanjangud
    • , H. Carl LeKaye
    • , Cameron Brennan
    • , Justin Cross
    • , Jason T. Huse
    • , Neil L. Kelleher
    • , Pavel Osten
    • , Craig B. Thompson
    •  & Timothy A. Chan

    Nature Genetics (2018)

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.