IMPAIRED CEREBRAL-CORTEX DEVELOPMENT AND BLOOD-PRESSURE REGULATION INFGF-2-DEFICIENT MICE

Fibroblast growth factor-2 (FGF-2) has been implicated in various sign aling processes which control embryonic growth and differentiation, ad ult physiology and pathology, To analyze the in vivo functions of this signaling molecule, the FGF-2 gene was inactivated by homologous reco mbination in mouse embryonic stem cells, FGF-2-deficient mice are viab le, but display cerebral cortex defects at birth. Bromodeoxyuridine pu lse labeling of embryos showed that proliferation of neuronal progenit ors is normal, whereas a fraction of them fail to colonize their targe t layers in the cere A corresponding reduction in parvalbumin-positive neurons is observed in adult cortical layers. Neuronal defects are no t limited to the cerebral cortex, as ectopic parvalbumin-positive neur ons are present in the hippocampal commissure and neuronal deficiencie s are observed in the cervical spinal cord. Physiological studies show ed that FGF-2-deficient adult mice are hypotensive. They respond norma lly 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 e ssential for their proliferation, The observed autonomic dysfunction i n FGF-2-deficient adult mice uncovers more general roles in neural dev elopment and function.