QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 29, 2003, 23(30):9862-9872

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (28) Citing Articles via Google Scholar Google Scholar Articles by Gulacsi, A. Articles by Lillien, L. Search for Related Content PubMed PubMed Citation Articles by Gulacsi, A. Articles by Lillien, L.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Sonic Hedgehog and Bone Morphogenetic Protein Regulate Interneuron Development from Dorsal Telencephalic Progenitors In Vitro

Alexandra Gulacsi and Laura Lillien

Department of Neurobiology and Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

Cortical progenitors are competent to produce interneurons, but do not generate large numbers of interneurons in vivo under normal circumstances. This could reflect the absence of an inductive signal in the environment of the dorsal telencephalon and/or the presence of an inhibitory signal. To determine whether either or both mechanisms regulate interneuron generation, progenitors in dorsomedial and dorsolateral wall explants of mouse telencephalon were marked with a retrovirus and cultured under several conditions. When cultured separately, progenitors in dorsomedial wall explants produced fewer GABAergic interneurons than progenitors in dorsolateral wall explants. When cocultured with ventral telencephalic cells, however, dorsomedial wall progenitors produced more GABAergic interneurons than in dorsomedial wall explants alone. The inductive effect of ventral telencephalon depended on sonic hedgehog (Shh) and could be mimicked by exogenous Shh. In contrast, exogenous bone morphogenetic protein 4 (BMP4) reduced the production of interneurons in dorsolateral wall explants and inhibited the induction by exogenous Shh. Moreover, inhibiting BMP signaling in dorsomedial wall progenitors with a dominant-negative BMP receptor Ib (dnBMPIb) virus increased their production of interneurons, even if Shh was blocked. Shh and dnBMPRIb increased proliferation and the generation of interneurons, but FGF2 did not induce interneurons, although it increased proliferation. This suggests that proliferation per se does not control the production of interneurons. Our findings suggest that the generation of interneurons by dorsal telencephalic progenitors is normally limited by excess levels of BMPs. Shh may promote the generation of interneurons by antagonizing BMP, but may not be required directly for the generation of interneurons.

Key words: cortex; progenitor; FGF; glutamate; GABA; neuronal differentiation

---

Received July 9, 2003; revised September 18, 2003; accepted September 22, 2003.

This article has been cited by other articles:

				A. Mukhopadhyay, T. McGuire, C.-Y. Peng, and J. A. Kessler Differential effects of BMP signaling on parvalbumin and somatostatin interneuron differentiation Development, August 1, 2009; 136(15): 2633 - 2642. [Abstract] [Full Text] [PDF]

				N.-E. Szabo, T. Zhao, X. Zhou, and G. Alvarez-Bolado The Role of Sonic Hedgehog of Neural Origin in Thalamic Differentiation in the Mouse J. Neurosci., February 25, 2009; 29(8): 2453 - 2466. [Abstract] [Full Text] [PDF]

				M. Fogarty, M. Grist, D. Gelman, O. Marin, V. Pachnis, and N. Kessaris Spatial Genetic Patterning of the Embryonic Neuroepithelium Generates GABAergic Interneuron Diversity in the Adult Cortex J. Neurosci., October 10, 2007; 27(41): 10935 - 10946. [Abstract] [Full Text] [PDF]

				C. Metin, C. Alvarez, D. Moudoux, T. Vitalis, C. Pieau, and Z. Molnar Conserved pattern of tangential neuronal migration during forebrain development Development, August 1, 2007; 134(15): 2815 - 2827. [Abstract] [Full Text] [PDF]

				J. Samanta, G. M. Burke, T. McGuire, A. J. Pisarek, A. Mukhopadhyay, Y. Mishina, and J. A. Kessler BMPR1a Signaling Determines Numbers of Oligodendrocytes and Calbindin-Expressing Interneurons in the Cortex J. Neurosci., July 11, 2007; 27(28): 7397 - 7407. [Abstract] [Full Text] [PDF]

				R. E. Ventura and J. E. Goldman Dorsal Radial Glia Generate Olfactory Bulb Interneurons in the Postnatal Murine Brain J. Neurosci., April 18, 2007; 27(16): 4297 - 4302. [Abstract] [Full Text] [PDF]

				Q. Xu, C. P. Wonders, and S. A. Anderson Sonic hedgehog maintains the identity of cortical interneuron progenitors in the ventral telencephalon Development, November 15, 2005; 132(22): 4987 - 4998. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help