Fibroblast growth factor receptor 1 is required for the proliferation of hippocampal progenitor cells and for hippocampal growth in mouse
Fibroblast growth factor receptor 1 is required for the proliferation of hippocampal progenitor cells and for hippocampal growth in mouse
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DOI：
10.1523/jneurosci.1140-04.2004
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发表时间：
2004-07-07
影响因子：
5.3
通讯作者：
Vaccarino, FM
中科院分区：
文献类型：
--
作者：
Ohkubo, Y;Uchida, AO;Vaccarino, FM
成纤维细胞生长因子受体1 （Fgfr1）在海马原基的心室区（VZ）祖细胞中高水平表达。为了研究Fgfr1在这些细胞中的作用，使用人胶质纤维酸性蛋白启动子，将“floxed”Fgfr1等位基因的体内Cre重组定向到放射状胶质谱系的细胞。海马VZ区的放射状胶质样细胞是锥体神经元和海马齿状回颗粒细胞的祖细胞。在该谱系的细胞中携带零Fgfr1等位基因（Fgfr1(Deltaflox)）的小鼠在整个胚胎背端脑中表现出Fgfr1基因表达的显著缺失。这些Fgfr1（Deltaflox）小鼠在胚胎后期海马VZ和DG的放射状胶质祖细胞分裂减少了30%，在出生时减少了50-60%，细胞存活率没有任何变化。此外，从Fgfr1（Deltaflox）海马神经上皮中无法分离到fgf2敏感的神经干细胞，而表皮生长因子敏感的神经干细胞不受影响。从围产期到成年，海马锥体神经元和DG颗粒细胞的数量减少了30-50%，DG和锥体细胞区含有小蛋白的中间神经元的数量也同样减少。我们得出结论，Fgfr1对海马生长是必要的，因为它在发育过程中促进海马祖细胞和干细胞的增殖。
Fibroblast growth factor receptor 1 (Fgfr1) is expressed at high levels by progenitor cells of the ventricular zone (VZ) within the hippocampal primordium. To investigate the role of Fgfr1 in these cells, in vivo Cre recombination of "floxed" Fgfr1 alleles was directed to cells of the radial glial lineage by using the human glial fibrillary acidic protein promoter. Radial glial-like cells of the hippocampal VZ are the progenitors of pyramidal neurons and granule cells of hippocampal dentate gyrus (DG). Mice carrying null Fgfr1 alleles (Fgfr1(Deltaflox)) in cells of this lineage showed a dramatic loss of Fgfr1 gene expression throughout the embryonic dorsal telencephalon. These Fgfr1(Deltaflox) mice exhibited a similar to30% decrease in dividing radial glial progenitor cells in the hippocampal VZ and DG in the late embryonic period, progressing to a similar to50-60% loss at birth, without any changes in cell survival. In addition, no FGF2-sensitive neural stem cells could be isolated from the Fgfr1(Deltaflox) hippocampal neuroepithelium, whereas epidermal growth factor-sensitive neural stem cells were not affected. The number of hippocampal pyramidal neurons and DG granule cells was similar to30-50% decreased from the perinatal period through adulthood, and the number of parvalbumin-containing interneurons was similarly decreased in both the DG and pyramidal cell fields. We conclude that Fgfr1 is necessary for hippocampal growth, because it promotes the proliferation of hippocampal progenitors and stem cells during development.