Neuronal defects and delayed wound healing in mice lacking fibroblast growth factor 2
Neuronal defects and delayed wound healing in mice lacking fibroblast growth factor 2
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DOI：
10.1073/pnas.95.10.5672
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发表时间：
1998-05-12
影响因子：
11.1
通讯作者：
Basilico, C
中科院分区：
文献类型：
--
作者：
Ortega, S;Ittmann, M;Basilico, C
碱性成纤维细胞生长因子（bFGF 2）是一种广谱的促有丝分裂、血管生成和神经营养因子，其在许多组织和细胞类型中以低Bevel表达，并在脑和垂体中达到高浓度，FGF 2已涉及许多生理和病理过程，包括肢体发育、血管生成、伤口愈合和肿瘤生长，但其生理作用仍不清楚，为了确定FGF 2在体内的功能，我们通过胚胎干细胞同源重组产生了缺乏所有三种FGF 2同种型的FGF 2敲除小鼠。FGF 2（-/-）小鼠是可存活的、可生育的，并且通过大体检查在表型上与FGF 2（+/+）同窝出生的小鼠无法区分。然而，可以通过组织学和免疫组织化学方法检测新皮质的细胞结构异常，在额叶运动感觉区中最明显。在FGF 2（-/-）小鼠的运动皮质的大多数层中观察到神经元密度的显著降低，其中V层受影响最大。在脑的其他区域如纹状体和海马中细胞密度是正常的。此外，在缺乏FGF 2的小鼠中，切除皮肤伤口的愈合延迟。这些结果表明，FGF 2，虽然不是胚胎发育所必需的，但在小鼠的皮质神经发生和皮肤伤口愈合中起着特定的作用，尽管FGF信号传导明显冗余，但不能由其他FGF家族成员进行。
Basic fibroblast growth factor (FGF2) is a wide-spectrum mitogenic, angiogenic, and neurotrophic factor that is expressed at low Bevels in many tissues and cell types and reaches high concentrations in brain and pituitary, FGF2 has been implicated in a multitude of physiological and pathological processes, including limb development, angiogenesis, wound healing, and tumor growth, but its physiological role is still unclear, To determine the function of FGF2 in vivo, we have generated FGF2 knockout mice, lacking ail three FGF2 isoforms, by homologous recombination ire embryonic stem cells. FGF2(-/-) mice are viable, fertile and phenotypically indistinguishable from FGF2(+/+) littermates by gross examination, However, abnormalities ire the cytoarchitecture of the neocortex, most pronounced in the frontal motor-sensory area, can be detected by histological and immunohistochemical methods. A significant reduction in neuronal density is observed in most layers of the motor cortex in the FGF2(-/-) mice, with layer V being the most affected, Cell density is normal in other regions of the brain such as the striatum and the hippocampus. In addition, the healing of excisional skin wounds is delayed in mice lacking FGF2. These results indicate that FGF2, although not essential for embryonic development, plays a specific role in cortical neurogenesis and skin wound healing in mice, which, in spite of the apparent redundancy of FGF signaling, cannot be carried out by other FGF family members.