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Dev Biol. 2008 Jan 1;313(1):35-46. Epub 2007 Nov 19.

Generation of Cajal-Retzius neurons in mouse forebrain is regulated by transforming growth factor beta-Fox signaling pathways.

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  • 1Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, Syracuse, NY 13210, USA.

Abstract

The generation of Cajal-Retzius (CR) neurons is restricted to discrete sites in the telencephalon. Most of these sites do not express Foxg1, a transcription factor that inhibits transforming growth factor (TGF)beta-dependent upregulation of p21. We tested the hypothesis that TGFbeta signaling triggers CR neurogenesis in Foxg1-deficient zones through p21 induction. In Foxg1(+/+) mice, p21 (a) was expressed in select cycling cells in CR neuron-producing areas and (b) was co-localized in newly generated CR neurons. Zones of CR neuronal production and p21 expression were expanded in the forebrains of Foxg1(Cre/Cre) mice. Manipulation of TGFbeta signaling in explants from cortical hems of wild-type mice altered p21 expression and the production of CR neurons. Furthermore, despite continued TGFbeta activity, p21 immunoreactivity diminished in CR neurons with distance from their generation site. This implicated a second pathway controlling p21 expression. We provide evidence that Foxo3a, which has been shown to translocate into the nucleus to act as a transcriptional co-activator of TGFbeta-dependent upregulation of p21, is strategically expressed to be involved in controlling p21 expression in CR neurons. Specifically, Foxo3a was nuclear in p21+/reelin+ cells in sites of CR neuronal generation, however, nuclear Foxo3a immunoreactivity was absent in p21-/reelin+ cells distal from sites of CR neurogenesis. Thus, TGFbeta and Foxo3a may work in concert to regulate expression of p21 during CR neuronal generation.

PMID:
18005957
PMCID:
PMC2278013
DOI:
10.1016/j.ydbio.2007.09.036
[PubMed - indexed for MEDLINE]
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