Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar development.
Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar development.
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DOI：
10.1016/j.mcn.2010.11.005
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发表时间：
2011-02
影响因子：
3.5
通讯作者：
Friedel, Roland H.
中科院分区：
文献类型：
--
作者：
Maier, Viola;Jolicoeur, Christine;Rayburn, Helen;Takegahara, Noriko;Kumanogoh, Atsushi;Kikutani, Hitoshi;Tessier-Lavigne, Marc;Wurst, Wolfgang;Friedel, Roland H.
信号蛋白和丛蛋白是同源的配体受体家族，在神经系统发育过程中调节重要步骤。丛蛋白b2受体在神经管闭合和小脑颗粒细胞发育中起着至关重要的作用，然而，其特异性配体仅在体外研究中被发现。在这里，我们通过体内和体外分析表明，两个Semaphorin-4家族成员Sema4C和Sema4G可能是Plexin-B2的体内配体。Sema4C和Sema4G基因在发育中的小脑皮层中表达，Sema4C和Sema4G蛋白特异性结合表达Plexin-B2的小脑颗粒细胞。为了进一步阐明它们在体内的功能，我们生成并分析了Sema4C和Sema4G敲除小鼠突变体。与Plexin-B2−/−突变体一样，Sema4C−/−突变体表现出脑外畸形和随后的新生儿死亡率，具有部分外显性。绕过畸形的Sema4C - / -突变体是存活和可育的，但表现出小脑颗粒细胞层的独特缺陷，包括吻侧小叶的间隙、尾侧小叶的融合和分子层的异位颗粒细胞。除了神经元缺陷外，我们在Sema4C−/−突变体中还观察到与Plexin-B2−/−突变体相似的腹侧皮肤色素沉着缺陷。Sema4G基因缺失本身不会引起明显的表型，但Sema4C和Sema4G基因的联合缺失会导致小脑表型的增强。然而，Sema4C/Sema4G双突变体的小脑表型总体上不如Plexin-B2−/−突变体严重，这表明存在更多的Plexin-B2配体。在发育中的小脑皮层外植体培养中，Sema4C以丛蛋白b2依赖的方式促进了小脑颗粒细胞前体的迁移，支持了颗粒细胞前体迁移速率降低是Sema4C - / -和Sema4C/Sema4G突变体小脑缺陷的基础的模型。
Semaphorins and Plexins are cognate ligand-receptor families that regulate important steps during nervous system development. The Plexin-B2 receptor is critically involved in neural tube closure and cerebellar granule cell development, however, its specific ligands have only been suggested by in vitro studies. Here, we show by in vivo and in vitro analyses that the two Semaphorin-4 family members Sema4C and Sema4G are likely to be in vivo ligands of Plexin-B2. The Sema4C and Sema4G genes are expressed in the developing cerebellar cortex, and Sema4C and Sema4G proteins specifically bind to Plexin-B2 expressing cerebellar granule cells. To further elucidate their in vivo function, we have generated and analyzed Sema4C and Sema4G knock-out mouse mutants. Like Plexin-B2−/− mutants, Sema4C−/− mutants reveal exencephaly and subsequent neonatal lethality with partial penetrance. Sema4C−/− mutants that bypass exencephaly are viable and fertile, but display distinctive defects of the cerebellar granule cell layer, including gaps in rostral lobules, fusions of caudal lobules, and ectopic granule cells in the molecular layer. In addition to neuronal defects, we observed in Sema4C−/− mutants also ventral skin pigmentation defects that are similar to those found in Plexin-B2−/− mutants. The Sema4G gene deletion causes no overt phenotype by itself, but combined deletion of Sema4C and Sema4G revealed an enhanced cerebellar phenotype. However, Sema4C/Sema4G double mutants showed overall less severe cerebellar phenotypes than Plexin-B2−/− mutants, indicating that further ligands of Plexin-B2 exist. In explant cultures of the developing cerebellar cortex, Sema4C promoted migration of cerebellar granule cell precursors in a Plexin-B2-dependent manner, supporting the model that a reduced migration rate of granule cell precursors is the basis for the cerebellar defects of Sema4C−/− and Sema4C/Sema4G mutants.
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影响因子：
--
作者：
Fazzari P;Penachioni J;Gianola S;Rossi F;Eickholt BJ;Maina F;Alexopoulou L;Sottile A;Comoglio PM;Flavell RA;Tamagnone L
通讯作者：
Tamagnone L
影响因子：
7.8
作者：
Giacobini, Paolo;Messina, Andrea;Morello, Francesca;Ferraris, Nicoletta;Corso, Simona;Penachioni, Junia;Giordano, Silvia;Tamagnone, Luca;Fasolo, Aldo
通讯作者：
Fasolo, Aldo
影响因子：
4.8
作者：
Basile, John R.;Gavard, Julie;Gutkind, J. Silvio
通讯作者：
Gutkind, J. Silvio
影响因子：
5.3
作者：
Deng, Suhua;Hirschberg, Alexandra;Kuner, Rohini
通讯作者：
Kuner, Rohini
影响因子：
3.5
作者：
INAGAKI, S;FURUYAMA, T;IWAHASHI, Y
通讯作者：
IWAHASHI, Y