ABSTRACT
We examined the role of the orphan nuclear hormone receptor CoupTFI in mediating cortical development downstream of meningeal retinoic acid signaling. CoupTFI is a regulator of cortical development known to collaborate with retinoic acid (RA) signaling in other systems. To examine the interaction of CoupTFI and cortical RA signaling we utilized Foxc1-mutant mice in which defects in meningeal development lead to alterations in cortical development due to a reduction of RA signaling. By analyzing CoupTFI(-/-);Foxc1(H/L) double mutant mice we provide evidence that CoupTFI is required for RA rescue of the ventricular zone and the neurogenic phenotypes in Foxc1-mutants. We also found that overexpression of CoupTFI in Foxc1-mutants is sufficient to rescue the Foxc1-mutant cortical phenotype in part. These results suggest that CoupTFI collaborates with RA signaling to regulate both cortical ventricular zone progenitor cell behavior and cortical neurogenesis.
Subject(s)
COUP Transcription Factor I/metabolism , Cerebral Cortex/embryology , Gene Expression Regulation, Developmental , Tretinoin/metabolism , Animals , Forkhead Transcription Factors/genetics , Genotype , Meninges/embryology , Mice , Mutation , Neurogenesis/physiology , Neurons/metabolism , Phenotype , Signal Transduction , Stem Cells/cytology , Time FactorsABSTRACT
Components of the Wnt signaling pathway are expressed in a tightly regulated and spatially specific manner during development of the forebrain, and Wnts are key regulators of regional forebrain identity. Wnt signaling from the cortical hem regulates the expansion and cell-type specification of the adjacent neuroepithelium and, in conjunction with Bmp, Fgf, and Shh signaling, controls dorsal-ventral forebrain patterning. Subsequently, Wnt signaling dynamically regulates the behavior of cortical progenitor cells, initially promoting the expansion of radial glia progenitor cells and later inducing neurogenesis by promoting terminal differentiation of intermediate progenitor cells. A role for Wnt signaling in cell-type specification has also been proposed.
