Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A neuronal migratory pathway crossing from diencephalon to telencephalon populates amygdala nuclei

Abstract

Neurons usually migrate and differentiate in one particular encephalic vesicle. We identified a murine population of diencephalic neurons that colonized the telencephalic amygdaloid complex, migrating along a tangential route that crosses a boundary between developing brain vesicles. The diencephalic transcription factor OTP was necessary for this migratory behavior.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: OTP expression during embryonic development.
Figure 2: Characterization of the OTP-expressing amygdaloid cells.
Figure 3: Cell migration from the hypothalamus to the amygdala.
Figure 4: Cellular migration from the hypothalamus to the amygdala.
Figure 5: Diencephalic migratory cells express OTP (red).
Figure 6: OTP-silenced cells failed to colonize the telencephalon.
Figure 7: Failure of OTP-expressing cells to migrate in Otp−/− embryos.
Figure 8: Altered patterning of the amygdala in Otp−/− embryos.

References

  1. 1

    Swanson, L.W. & Petrovich, G.D. What is the amygdala? Trends Neurosci. 21, 323–331 (1998).

    CAS  Article  Google Scholar 

  2. 2

    Alheid, G.F. & Heimer, L. New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid and corticopetal components of substantia innominata. Neuroscience 27, 1–39 (1988).

    CAS  Article  Google Scholar 

  3. 3

    Cassell, M.D., Freedman, L.J. & Shi, C. The intrinsic organization of the central extended amygdala. Ann. NY Acad. Sci. 877, 217–241 (1999).

    CAS  Article  Google Scholar 

  4. 4

    Shammah-Lagnado, S.J. et al. Supracapsular bed nucleus of the stria terminalis contains central and medial extended amygdala elements: evidence from anterograde and retrograde tracing experiments in the rat. J. Comp. Neurol. 422, 533–555 (2000).

    CAS  Article  Google Scholar 

  5. 5

    Holmgren, N. Points of view concerning forebrain morphology in higher vertebrates. Acta Zool. 6, 413–447 (1925).

    Article  Google Scholar 

  6. 6

    Swanson, L.W. Cerebral hemisphere regulation of motivated behavior. Brain Res. 886, 113–164 (2000).

    CAS  Article  Google Scholar 

  7. 7

    Puelles, L. Brain segmentation and forebrain development in amniotes. Brain Res. Bull. 55, 695–710 (2001).

    CAS  Article  Google Scholar 

  8. 8

    Martínez-García, F., Martínez-Marcos, A. & Lanuza, E. The pallial amygdala of amniote vertebrates: evolution of the concept, evolution of the structure. Brain Res. Bull. 57, 463–469 (2002).

    Article  Google Scholar 

  9. 9

    Medina, L., Brox, A., Legaz, I., García-López, M. & Puelles, L. Expression patterns of developmental regulatory genes show comparable divisions in the telencephalon of Xenopus and mouse: insights into the evolution of the forebrain. Brain Res. Bull. 66, 297–302 (2005).

    CAS  Article  Google Scholar 

  10. 10

    Tole, S., Remedios, R., Saha, B. & Stoykova, A. Selective requirement of Pax6, but not Emx2, in the specification and development of several nuclei of the amygdaloid complex. J. Neurosci. 25, 2753–2760 (2005).

    CAS  Article  Google Scholar 

  11. 11

    Puelles, L. et al. Pallial and subpallial derivatives in the embryonic chick and mouse telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6 and Tbr-1. J. Comp. Neurol. 424, 409–438 (2000).

    CAS  Article  Google Scholar 

  12. 12

    Medina, L. et al. Expression of Dbx1, Neurogenin 2, Semaphorin 5A, Cadherin 8 and Emx1 distinguish ventral and lateral pallial histogenetic divisions in the developing mouse claustroamygdaloid complex. J. Comp. Neurol. 474, 504–523 (2004).

    Article  Google Scholar 

  13. 13

    Flames, N. et al. Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J. Neurosci. 27, 9682–9695 (2007).

    CAS  Article  Google Scholar 

  14. 14

    García-López, M. et al. Histogenetic compartments of the mouse centromedial and extended amygdala based on gene expression patterns during development. J. Comp. Neurol. 506, 46–74 (2008).

    Article  Google Scholar 

  15. 15

    Canteras, N.S., Simerly, R.B. & Swanson, L.W. Organization of projections from the medial nucleus of the amygdala: a PHAL study in the rat. J. Comp. Neurol. 360, 213–245 (1995).

    CAS  Article  Google Scholar 

  16. 16

    Stenman, J., Toresson, H. & Campbell, K. Identification of two distinct progenitor populations in the lateral ganglionic eminence: implications for striatal and olfactory bulb neurogenesis. J. Neurosci. 23, 167–174 (2003).

    CAS  Article  Google Scholar 

  17. 17

    Wang, W. & Lufkin, T. The murine Otp homeobox gene plays an essential role in the specification of neuronal cell lineages in the developing hypothalamus. Dev. Biol. 227, 432–449 (2000).

    CAS  Article  Google Scholar 

  18. 18

    Bardet, S.M., Martínez-de-la-Torre, M., Northcutt, R.G., Rubenstein, J.L.R. & Puelles, L. Conserved pattern of OTP-positive cells in the paraventricular nucleus and other hypothalamic sites of tetrapods. Brain Res. Bull. 75, 231–235 (2008).

    CAS  Article  Google Scholar 

  19. 19

    Michaud, J.L., Rosenquist, T., May, N.R. & Fan, C.M. Development of neuroendocrine lineages requires the bHLH-PAS transcription factor SIM1. Genes Dev. 12, 3264–3275 (1998).

    CAS  Article  Google Scholar 

  20. 20

    Nakai, S. et al. The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse. Genes Dev. 9, 3109–3121 (1995).

    CAS  Article  Google Scholar 

  21. 21

    Fan, C.M. et al. Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of Down syndrome. Mol. Cell. Neurosci. 7, 1–16 (1996).

    CAS  Article  Google Scholar 

  22. 22

    Sheng, H.Z. et al. Expression of murine Lhx5 suggests a role in specifying the forebrain. Dev. Dyn. 208, 266–277 (1997).

    CAS  Article  Google Scholar 

  23. 23

    Puelles, L. & Rubenstein, J.L.R. Forebrain gene expression domains and the evolving prosomeric model. Trends Neurosci. 26, 469–476 (2003).

    CAS  Article  Google Scholar 

  24. 24

    Simeone, A. et al. Orthopedia, a novel homeobox-containing gene expressed in the developing CNS of both mouse and Drosophila. Neuron 13, 83–101 (1994).

    CAS  Article  Google Scholar 

  25. 25

    Blechman, J. et al. Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia. Development 134, 4417–4426 (2007).

    CAS  Article  Google Scholar 

  26. 26

    Acampora, D. et al. Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene. Genes Dev. 13, 2787–2800 (1999).

    CAS  Article  Google Scholar 

  27. 27

    Acampora, D., Postiglione, M.P., Avantaggiato, V., Bonito, M.D. & Simeone, A. The role of Otx and Otp genes in brain development. Int. J. Dev. Biol. 44, 669–677 (2000).

    CAS  PubMed  Google Scholar 

  28. 28

    Altman, J. & Bayer, S.A. Development of the diencephalon in the rat. I. Autoradiographic study of the time of origin and settling patterns of neurons of the hypothalamus. J. Comp. Neurol. 182, 945–971 (1978a).

    CAS  Article  Google Scholar 

  29. 29

    Altman, J. & Bayer, S.A. Development of the diencephalon in the rat. II. Correlation of the embryonic development of the hypothalamus with the time of origin of its neurons. J. Comp. Neurol. 182, 973–993 (1978b).

    CAS  Article  Google Scholar 

  30. 30

    Swanson, L.W. Development of the paraventricular nucleus of the hypothalamus. in From Development to Degeneration and Regeneration of the Nervous System (eds. Ribak, C.E., Arámburo-de la Hoz, C., Jones, E.G., Larriva-Sahd, J.A. & Swanson, L.W.) 69–84 (Oxford University Press, Oxford, 2009).

  31. 31

    Ryu, S. et al. Orthopedia homeodomain protein is essential for diencephalic dopaminergic neuron development. Curr. Biol. 17, 873–880 (2007).

    CAS  Article  Google Scholar 

  32. 32

    Choi, G.B. et al. Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus. Neuron 46, 647–660 (2005).

    CAS  Article  Google Scholar 

  33. 33

    Remedios, R., Subramanian, L. & Tole, S. LIM genes parcellate the embryonic amygdala and regulate its development. J. Neurosci. 24, 6986–6990 (2004).

    CAS  Article  Google Scholar 

  34. 34

    Letinic, K. & Rakic, P. Telencephalic origin of human thalamic GABAergic neurons. Nat. Neurosci. 4, 931–936 (2001).

    CAS  Article  Google Scholar 

  35. 35

    Rakic, P. Principles of neural cell migration. Experientia 46, 882–891 (1990).

    CAS  Article  Google Scholar 

  36. 36

    De Carlos, J.A., López-Mascaraque, L. & Valverde, F. Dynamics of cell migration from the lateral ganglionic eminence in the rat. J. Neurosci. 16, 6146–6156 (1996).

    CAS  Article  Google Scholar 

  37. 37

    Anderson, S., Mione, M., Yun, K. & Rubenstein, J.L. Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis. Cereb. Cortex 9, 646–654 (1999).

    CAS  Article  Google Scholar 

  38. 38

    Lavdas, A.A., Grigoriou, M., Pachnis, V. & Parnavelas, J.G. The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. J. Neurosci. 19, 7881–7888 (1999).

    CAS  Article  Google Scholar 

  39. 39

    Wichterle, H., Turnbull, D.H., Nery, S., Fishell, G. & Alvarez-Buylla, A. In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain. Development 128, 3759–3771 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Zhao, T. et al. Genetic mapping of Foxb1 cell lineage shows migration from caudal diencephalon to telencephalon and lateral hypothalamus. Eur. J. Neurosci. 28, 1941–1955 (2008).

    Article  Google Scholar 

  41. 41

    Soma, M. et al. Development of the mouse amygdala as revealed by enhanced green fluorescent protein gene transfer by means of in utero electroporation. J. Comp. Neurol. 513, 113–128 (2009).

    CAS  Article  Google Scholar 

  42. 42

    Hirata, T. et al. Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala. Nat. Neurosci. 12, 141–149 (2009).

    CAS  Article  Google Scholar 

  43. 43

    García-Moreno, F., López-Mascaraque, L. & De Carlos, J.A. Early telencephalic migration topographically converging in the olfactory cortex. Cereb. Cortex 18, 1239–1252 (2008).

    Article  Google Scholar 

  44. 44

    Caqueret, A., Boucher, F. & Michaud, J.L. Laminar organization of the early developing anterior hypothalamus. Dev. Biol. 298, 95–106 (2006).

    CAS  Article  Google Scholar 

  45. 45

    García-Moreno, F., López-Mascaraque, L. & De Carlos, J.A. Origins and migratory routes of murine Cajal-Retzius cells. J. Comp. Neurol. 500, 419–432 (2007).

    Article  Google Scholar 

  46. 46

    Valverde, F. The Golgi method. A tool for comparative structural analyses. in Contemporary Research Methods in Neuroanatomy (eds Nauta, W.J.H. & Ebbensson, S.O.E.) 12–31 (Springer, New York, 1970).

Download references

Acknowledgements

We thank J. Lerma, A. Nieto, M.L. Ceci, A. Blanchart and J. García-Marqués for helpful comments; P. Bovolenta and C. Sánchez-Camacho for their kind gift of the pCAG plasmid; F. Vaccarino and G. Corte for the generous gift of antibodies to Otp and Foxg1; L. Menéndez de la Prida for providing the GAD-GFP transgenic mice; A. Kastanauskaite and L. María Suarez for their help with the intracellular injections of Lucifer Yellow and M. Sefton for editorial assistance. This work was supported by grants from the Ministerio de Ciencia e Innovación (BFU2007-60351/BFI), the OLFACTOSENSE Consortium of the Comunidad Autónoma de Madrid (P-SEM-0255-2006) and the Castilla-La Mancha Health Research Foundation (FISCAM PI2007-66) to J.A.DC., and the FP6 for the EUTRACC Integrate Project (LSHG-CT-2007-037445), the 'Stem Cell Project' of Fondazione Roma and the Italian Association for Cancer Research to A.S. Funding for M.P. was provided by Fundación Centro de Investigaciones de Enfermedades Neurológicas (PI006-08).

Author information

Affiliations

Authors

Contributions

J.A.D.C., L.L.-M. and F.G.-M. planned the experiments. F.G.-M. and M.P. carried out the experiments and analyzed the data. A.S., L.G.D.G. and M.D.S. performed and analyzed most of the experiments on Otp mutant mice. J.A.D.C. and F.G.-M. discussed the results and wrote the paper.

Corresponding author

Correspondence to Juan A De Carlos.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–11 (PDF 10115 kb)

Supplementary Movie 1

Ecographic visualization of in utero injection. (MOV 1425 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

García-Moreno, F., Pedraza, M., Di Giovannantonio, L. et al. A neuronal migratory pathway crossing from diencephalon to telencephalon populates amygdala nuclei. Nat Neurosci 13, 680–689 (2010). https://doi.org/10.1038/nn.2556

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing