Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants.
The neocortex is divided into multiple areas with specific architecture, molecular identity and pattern of connectivity with the dorsal thalamus. Gradients of transcription factor expression in the cortical primordium regulate molecular regionalization and potentially the patterning of thalamic projections. We show that reduction of Fgf8 levels in hypomorphic mouse mutants shifts early gradients of gene expression rostrally, thereby modifying the molecular identity of rostral cortical progenitors. This shift correlates with a reduction in the size of a molecularly defined rostral neocortical domain and a corresponding rostral expansion of more caudal regions. Despite these molecular changes, the topography of projections between the dorsal thalamus and rostral neocortex in mutant neonates appears the same as the topography of wild-type littermates. Overall, our study demonstrates the role of endogenous Fgf8 in regulating early gradients of transcription factors in cortical progenitor cells and in molecular regionalization of the cortical plate.
Garel
Sonia
S
Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, CA 94143-0984, USA.
Huffman
Kelly J
KJ
Rubenstein
John L R
JL
D000818:Animals; D051838:COUP Transcription Factor I; D002465:Cell Movement / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D019579:Neocortex / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C496457:Fgf8 protein, mouse; C497590:Nr2f1 protein, mouse