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−/−;Foxc1H/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.
Highlights
During cortical development neurons are produced in a tightly regulated manner from progenitor cells residing adjacent to the lateral ventricles
Because CoupTFI overexpression in the cortex increased retinoic acid (RA) signaling [17] and there is evidence that RA signaling may promote expression of CoupTFI and CoupTFII in other systems [28,29], we wondered whether dysregulated expression of CoupTFI in Foxc1-mutants might underlie aspects of the Foxc1 mutant phenotype
At E14.5 CoupTFI is expressed in a high-ventral to low-dorsal pattern in cortical progenitor cells in controls (Figure 2A, C, E)
Summary
During cortical development neurons are produced in a tightly regulated manner from progenitor cells residing adjacent to the lateral ventricles. In the developing cortex bipolar radial glia are the primary neurogenic stem cells. These bipolar cells span the cortical wall with cell bodies close to the ventricular surface and primary cilia projecting apically into the ventricle, receiving signals that promote radial glia proliferation [1,2]. Radial glia have basal processes projecting to the pial surface where the radial glia endfeet interact with the pial extracellular matrix [3,4]. Radial glia receive signaling cues from neighboring progenitor cells and differentiated neurons [6,7,8,9]. Numerous extrinsic signals from the surrounding environment during development impact the behavior of radial glia, collaboratively regulating their proliferative capacity and developmental maturation
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