Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice

被引:331
作者
Dono, R
Texido, G
Dussel, R
Ehmke, H
Zeller, R
机构
[1] European Mol Biol Lab, D-69117 Heidelberg, Germany
[2] Univ Heidelberg, Inst Physiol, D-69120 Heidelberg, Germany
关键词
autonomic dysfunction; blood pressure; cerebral cortex; FGF-2; neural development;
D O I
10.1093/emboj/17.15.4213
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 cere 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.
引用
收藏
页码:4213 / 4225
页数:13
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