This suggests that Unc5D/Dcc signaling is binary rather than grad

This suggests that Unc5D/Dcc signaling is binary rather than graded, which is consistent with it Androgen Receptor Antagonist mw playing a role in multipolar to radial phase transition but not chemotropic guidance. An area of future interest will be to investigate whether different ligands initiate distinct downstream signaling cascades upon Unc5D-activation. It is striking to compare the early role of FoxG1 demonstrated for suppressing

the production of Cajal-Retzius cells ( Hanashima et al., 2004, Hanashima et al., 2007 and Shen et al., 2006b) with our present finding that FoxG1 can suppress the late multipolar cell phase of postmitotic pyramidal neuron precursors ( Figure 6B). Although quite distinct lineages, Cajal-Retzius cells and pyramidal neuron precursors in the multipolar migratory phase have in common their expression of Reelin ( Uchida et al., 2009 and Yoshida et al., 2006) and their propensity for tangential migration. Interestingly, we observe a similar dynamic regulation of FoxG1 in telencephalic GABAergic interneuron precursors, where this gene is selectively downregulated during the tangential phase of their migration

and reinitiated when they have invaded the cortical plate (G.M., unpublished data and Figures S1A–S1C). Furthermore, FoxG1 is also essential for the integration of interneuron precursors into the cortical plate (G.M., unpublished data). Taken together, there may be a universal requirement for FoxG1 downregulation during the tangential phases of neuronal migration within the telencephalon. These findings lead us to conjecture that FoxG1 function has been evolutionarily adapted in mammals as a means to regulate radial versus tangential modes of neuronal migration and is therefore vital to the assembly of the laminar isothipendyl and columnar organization that is the hallmark of the cerebral cortex. See the Supplemental Experimental

Procedures. All animal handling and experiments were performed in accordance with protocols approved by local Institutional Animal Care and Use Committee of the NYU School of Medicine. Research in Fishell lab is supported by the National Institutes of Health (grants RO1NS039007 and RO1MH071679) and the Simons Foundation and New York State through its NYSTEM initiative. G.M. is supported by a grant from the National Alliance for Research on Schizophrenia and Depression. We thank the following doctors for kindly sharing their reagents: David Anderson (Neurog2-CreER driver), Yoshiki Sasai (FoxG1 antibodies), Sally Temple (FoxG1 antibodies), Jean Hebert (Targeting arms for the FoxG1 locus), Toshifumi Morimura (mDab1 DNA construct), Eseng Lai (FoxG1-LacZ knockin mutant), Pierre Mattar and Carol Schuurmans (NeuroD1 promoter pGL3 construct), Kyonsoo Hong (Rat Dcc DNA construct), Takahiko Matsuda and Connie Cepko (CAGEN vector), Rudiger Klein (Flrt1-3 DNA constructs), and Nobuhiko Yamamoto (Netrin4 DNA construct).

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