Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice.
Fibroblast growth factor-2 (FGF-2) has been implicated in various signaling processes which control embryonic growth and differentiation, adult physiology and pathology. To analyze the in vivo functions of this signaling molecule, the FGF-2 gene was inactivated by homologous recombination in mouse embryonic stem cells. FGF-2-deficient mice are viable, but display cerebral cortex defects at birth. Bromodeoxyuridine pulse labeling of embryos showed that proliferation of neuronal progenitors is normal, whereas a fraction of them fail to colonize their target layers in the cerebral cortex. A corresponding reduction in parvalbumin-positive neurons is observed in adult cortical layers. Neuronal defects are not limited to the cerebral cortex, as ectopic parvalbumin-positive neurons are present in the hippocampal commissure and neuronal deficiencies are observed in the cervical spinal cord. Physiological studies showed that FGF-2-deficient adult mice are hypotensive. They respond normally to angiotensin II-induced hypertension, whereas neural regulation of blood pressure by the baroreceptor reflex is impaired. The present genetic study establishes that FGF-2 participates in controlling fates, migration and differentiation of neuronal cells, whereas it is not essential for their proliferation. The observed autonomic dysfunction in FGF-2-deficient adult mice uncovers more general roles in neural development and function.
Dono
R
R
EMBL, Heidelberg, Germany.
Texido
G
G
Dussel
R
R
Ehmke
H
H
Zeller
R
R
D000818:Animals; D017704:Baroreflex / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D002540:Cerebral Cortex / Q000196:embryology* / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D006720:Homozygote; D007022:Hypotension / Q000196:embryology / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology
D016222:Fibroblast Growth Factor 2