FGF signalling generates ventral telencephalic cells independently of SHH

Abstract

Sonic hedgehog (SHH) is required to generate ventral cell types throughout the central nervous system. Its role in directly specifying ventral cells,however, has recently been questioned because loss of the Shh gene has little effect on ventral development if the Gli3 gene is also mutant. Consequently, another ventral determinant must exist. Here, genetic evidence establishes that FGFs are required for ventral telencephalon development. First, simultaneous deletion of Fgfr1 and Fgfr3specifically in the telencephalon results in the loss of differentiated ventromedial cells; and second, in the Fgfr1;Fgfr2 double mutant, ventral precursor cells are lost, mimicking the phenotype obtained previously with a loss of SHH signalling. Yet, in the Fgfr1;Fgfr2 mutant, Shh remains expressed, as does Gli1, the transcription of which depends on SHH activity, suggesting that FGF signalling acts independently of SHH to generate ventral precursors. Moreover, the Fgfr1;Fgfr2 phenotype, unlike the Shhphenotype, is not rescued by loss of Gli3, further indicating that FGFs act downstream of Shh and Gli3 to generate ventral telencephalic cell types.