Midline radial glia translocation and corpus callosum formation require FGF signaling.
Midline astroglia in the cerebral cortex develop earlier than other astrocytes through mechanisms that are still unknown. We show that radial glia in dorsomedial cortex retract their apical endfeet at midneurogenesis and translocate to the overlaying pia, forming the indusium griseum. These cells require the fibroblast growth factor receptor 1 (Fgfr1) gene for their precocious somal translocation to the dorsal midline, as demonstrated by inactivating the Fgfr1 gene in radial glial cells and by RNAi knockdown of Fgfr1 in vivo. Dysfunctional astroglial migration underlies the callosal dysgenesis in conditional Fgfr1 knockout mice, suggesting that precise targeting of astroglia to the cortex has unexpected roles in axon guidance. FGF signaling is sufficient to induce somal translocation of radial glial cells throughout the cortex; furthermore, the targeting of astroglia to dorsolateral cortex requires FGFr2 signaling after neurogenesis. Hence, FGFs have an important role in the transition from radial glia to astrocytes by stimulating somal translocation of radial glial cells.
Smith
Karen Müller
KM
Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Ohkubo
Yasushi
Y
Maragnoli
Maria Elisabetta
ME
Rasin
Mladen-Roko
MR
Schwartz
Michael L
ML
Sestan
Nenad
N
Vaccarino
Flora M
FM
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D003337:Corpus Callosum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
C496457:Fgf8 protein, mouse; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; C496356:Fgfr2 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2