Fgf10 regulates transition period of cortical stem cell differentiation to radial glia controlling generation of neurons and basal progenitors.
Radial glia (RG), the progenitors of cortical neurons and basal progenitors (BPs), differentiate from neuroepithelial cells (NCs) with stem cell properties. We show that the morphogen Fgf10 is transiently expressed by NCs coincident with the transition period of NC differentiation into RG. Targeted deletion of Fgf10 delays RG differentiation, whereas overexpression has opposing effects. Delayed RG differentiation in Fgf10 mutants occurs selectively in rostral cortex, paralleled by an extended period of symmetric NC divisions increasing progenitor number, coupled with delayed and initially diminished production of neurons and BPs. RG eventually differentiate in excess number and overproduce neurons and BPs rostrally resulting in tangential expansion of frontal areas and increased laminar thickness. Thus, transient Fgf10 expression regulates timely differentiation of RG, and through this function, determines both length of the early progenitor expansion phase and onset of neurogenesis and ultimately the number of progenitors and neurons fated to specific cortical areas.
Sahara
Setsuko
S
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
O'Leary
Dennis D M
DD
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000502:physiology*; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000172:deficiency / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy
C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine