Impaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice.
Impaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice.
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DOI：
10.1016/j.brainres.2012.04.002
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发表时间：
2012-06-15
期刊：
影响因子：
2.9
通讯作者：
Vaccarino FM
中科院分区：
文献类型：
--
作者：
Müller Smith K;Williamson TL;Schwartz ML;Vaccarino FM
成纤维细胞生长因子受体（FGFR）信号通过调节放射状胶质干细胞的扩增来决定大脑皮层的大小，并参与中线胶质结构的形成。我们表明，Fgfr 1和Fgfr 2双敲除（FGFR DKO）产生的Cre介导的重组驱动的人GFAP启动子（hGFAP），由于减少放射状神经胶质细胞和其他神经胶质细胞前体的增殖在胚胎晚期和新生儿FGFR DKO小鼠小脑的大小。EGL中颗粒祖细胞（GCPs）的增殖也减少，导致颗粒细胞数量减少。此外，颗粒细胞向内迁移到内部颗粒细胞层（IGL）和GABA中间神经元向外迁移到分子层（ML）被逮捕，破坏层和小叶形态。浦肯野神经元和它们的树突，这是不针对Cre介导的重组的Fgf受体，也错位FGFR DKO小鼠，可能是由于改变伯格曼神经胶质细胞的方向或减少颗粒细胞数量。我们的研究结果表明FGFR信号在小脑形态发生中的双重作用。第一个作用是扩大外部颗粒层中的颗粒神经元前体细胞和整个小脑中的神经胶质前体细胞的数量。第二是建立正确的Bergmann胶质细胞形态，这对颗粒细胞迁移至关重要。由FGFR信号传导丧失引起的破坏的小脑大小和层状结构损害FGFR DKO小鼠的运动学习和协调。
Fibroblast growth factor receptor (FGFR) signaling determines the size of the cerebral cortex by regulating the amplification of radial glial stem cells, and participates in the formation of midline glial structures. We show that Fgfr1 and Fgfr2 double knockouts (FGFR DKO) generated by Cre mediated recombination driven by the human GFAP promoter (hGFAP) have reduced cerebellar size due to reduced proliferation of radial glia and other glial precursors in late embryonic and neonatal FGFR DKO mice. The proliferation of granule cell progenitors (GCPs) in the EGL was also reduced, leading to reduced granule cell numbers. Furthermore, both inward migration of granule cells into the inner granule cell layer (IGL) and outward migration of GABA interneurons into the molecular layer (ML) were arrested, disrupting layer and lobular morphology. Purkinje neurons and their dendrites, which were not targeted by Cre mediated recombination of Fgf receptors, were also misplaced in FGFR DKO mice, possibly as a consequence of altered Bergmann glia orientation or reduced granule cell number. Our findings indicate a dual role for FGFR signaling in cerebellar morphogenesis. The first role is to amplify the number of granule neuron precursors in the external granular layer and glial precursor cells throughout the cerebellum. The second is to establish the correct Bergmann glia morphology, which is crucial for granule cell migration. The disrupted cerebellar size and laminar architecture resulting from loss of FGFR signaling impairs motor learning and coordination in FGFR DKO mice.
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DOI：
10.1523/jneurosci.4439-11.2011
发表时间：
2011-10-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Rash BG;Lim HD;Breunig JJ;Vaccarino FM
通讯作者：
Vaccarino FM
影响因子：
50.3
作者：
Schueller, Ulrich;Heine, Vivi M.;Mao, Junhao;Kho, Alvin T.;Dillon, Allison K.;Han, Young-Goo;Huillard, Emmanuelle;Sun, Tao;Ligon, Azra H.;Qian, Ying;Ma, Qiufu;Alvarez-Buylla, Arturo;McMahon, Andrew P.;Rowitch, David H.;Ligon, Keith L.
通讯作者：
Ligon, Keith L.
影响因子：
5.3
作者：
Ohkubo, Y;Uchida, AO;Vaccarino, FM
通讯作者：
Vaccarino, FM
影响因子：
16.2
作者：
Li, JYH;Lao, ZM;Joyner, AL
通讯作者：
Joyner, AL
DOI：
10.1073/pnas.87.12.4543
发表时间：
1990-06-01
影响因子：
11.1
作者：
GASSER, UE;HATTEN, ME
通讯作者：
HATTEN, ME