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Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice
Abstract:
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.
Insights
Fibroblast growth factor-2 (FGF-2) deficiency impairs neuronal development and migration, leading to brain defects and autonomic dysfunction in mice. This study highlights FGF-2
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Fibroblast growth factor-2 (FGF-2) is crucial for embryonic development, adult physiology, and pathology.
- Understanding FGF-2's in vivo functions is essential for elucidating its role in complex biological processes.
Purpose of the Study:
- To investigate the in vivo functions of Fibroblast growth factor-2 (FGF-2) by analyzing gene-deficient mice.
- To determine the specific roles of FGF-2 in neuronal cell fate, migration, proliferation, and differentiation.
- To assess the impact of FGF-2 deficiency on physiological functions, particularly blood pressure regulation.
Main Methods:
- Gene inactivation of FGF-2 in mouse embryonic stem cells using homologous recombination.
- Bromodeoxyuridine pulse labeling to track neuronal progenitor proliferation and migration in developing embryos.
- Histological analysis of brain and spinal cord tissues to identify neuronal abnormalities.
- Physiological studies to evaluate blood pressure regulation and baroreceptor reflex function in adult mice.
Main Results:
- FGF-2-deficient mice exhibit viable but display significant cerebral cortex defects at birth.
- Neuronal progenitor proliferation is normal, but migration to target layers is impaired, reducing parvalbumin-positive neurons.
- Neuronal defects extend beyond the cortex, with ectopic neurons in the hippocampal commissure and deficiencies in the cervical spinal cord.
- Adult FGF-2-deficient mice are hypotensive and show impaired neural regulation of blood pressure via the baroreceptor reflex.
Conclusions:
- FGF-2 is essential for controlling neuronal cell fate, migration, and differentiation, but not proliferation.
- FGF-2 plays a critical role in the development and function of the nervous system, including autonomic regulation.
- The study establishes FGF-2 as a key regulator in neural development and physiological homeostasis.