FGF signaling is strictly required to maintain early telencephalic precursor cell survival.
The FGF family of extracellular signaling factors has been proposed to play multiple roles in patterning the telencephalon, the precursor to the cerebrum. In this study, unlike previous ones, we effectively abolish FGF signaling in the anterior neural plate via deletion of three FGF receptor (FGFR) genes. Triple FGFR mutant mice exhibit a complete loss of the telencephalon, except the dorsal midline. Disruption of FGF signaling prior to and coincident with telencephalic induction reveals that FGFs promote telencephalic character and are strictly required to keep telencephalic cells alive. Moreover, progressively more severe truncations of the telencephalon are observed in FGFR single, double and triple mutants. Together with previous gain-of-function studies showing induction of Foxg1 expression and mirror-image duplications of the cortex by exogenous FGF8, our loss-of-function results suggest that, rather than independently patterning different areas, FGF ligands and receptors act in concert to mediate organizer activity for the whole telencephalon.
Paek
Hunki
H
Departments of Neuroscience and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Gutin
Grigoriy
G
Hébert
Jean M
JM
D000818:Animals; D019521:Body Patterning; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D054258:Neural Plate / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013687:Telencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D009419:Nerve Tissue Proteins; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors