Rostral-caudal distribution of Emx1-lineage stem/transit amplifying cells and lineage progression in embryonic cortex depend on Hedgehog signaling.

Lineage progression of neural precursors to an EGF-responsive state can be promoted by several extrinsic signals, including fibroblast growth factor 2 (FGF2) and Hedgehog (Hh). It has been suggested that EGF-responsive precursors in the embryonic cerebral cortex originate in the ventral telencephalon in an FGF-dependent manner and migrate dorsally. To determine whether cortical EGF-responsive cells originate locally from dorsal precursors, we marked these precursors using Emx1-cre and the cre reporter Z/EG and observed a local origin for EGF-responsive cells. We also found a rostral-caudal difference in the abundance of self-renewing, neurogenic Emx1-lineage precursors, with more present rostrally. Deleting the Hh receptor smoothened in Emx-1 lineage cells impaired their progression to an EGF-responsive state. Moreover, loss of smoothened increased the proportion of neurogenic, self-renewing Emx1-lineage cells in caudal regions of cortex, eliminating their asymmetric distribution. Our results support the idea that Hh signaling promotes lineage progression of stem/transit amplifying cells, particularly in caudal regions of the embryonic cortex, leading to rostral-caudal differences in the abundance of neurogenic, self-renewing precursors.