An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold.
An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold.
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DOI：
10.1371/journal.pbio.3002212
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发表时间：
2023-08
期刊：
影响因子：
9.8
通讯作者：
Riccomagno, Martin M.
中科院分区：
文献类型：
--
作者：
Wong, Wenny;Estep, Jason A.;Treptow, Alyssa M.;Rajabli, Niloofar;Jahncke, Jennifer N.;Ubina, Teresa;Wright, Kevin M.;Riccomagno, Martin M.
成熟的哺乳动物皮层由6个结构和功能不同的层组成。这种层状结构组装的两个关键步骤是胶质支架的初始建立和有丝分裂后神经元的迁移。这些过程包括精确和及时地调节神经细胞从基质上的粘附和脱离。尽管我们对粘附底物在神经元迁移和胶质支架形成过程中的作用了解甚多，但对这些信号如何在这些神经细胞中被解释和整合却知之甚少。在这里，我们提供了体内证据，证明Cas蛋白，一个细胞质适配器家族，在皮质层压过程中起着功能性和冗余的作用。Cas三重条件敲除（Cas TcKO）小鼠表现出严重的皮质表型，其特征为鹅卵石状畸形。分子上位性和遗传学实验表明，Cas蛋白以径向胶质细胞自主的方式作用于跨膜糖醛酸失调蛋白和β1-整合素的下游。总之，这些数据确立了Cas接头蛋白在皮层回路形成过程中新的重要作用，并揭示了控制皮层支架形成的信号轴。径向胶质支架的组装是皮层迁移的关键步骤；本研究表明，在这种胶质支架的建立过程中，Cas衔接蛋白作用于糖醛酸失调蛋白和b1-整合素的下游，以调节皮质层压。
The mature mammalian cortex is composed of 6 architecturally and functionally distinct layers. Two key steps in the assembly of this layered structure are the initial establishment of the glial scaffold and the subsequent migration of postmitotic neurons to their final position. These processes involve the precise and timely regulation of adhesion and detachment of neural cells from their substrates. Although much is known about the roles of adhesive substrates during neuronal migration and the formation of the glial scaffold, less is understood about how these signals are interpreted and integrated within these neural cells. Here, we provide in vivo evidence that Cas proteins, a family of cytoplasmic adaptors, serve a functional and redundant role during cortical lamination. Cas triple conditional knock-out (Cas TcKO) mice display severe cortical phenotypes that feature cobblestone malformations. Molecular epistasis and genetic experiments suggest that Cas proteins act downstream of transmembrane Dystroglycan and β1-Integrin in a radial glial cell-autonomous manner. Overall, these data establish a new and essential role for Cas adaptor proteins during the formation of cortical circuits and reveal a signaling axis controlling cortical scaffold formation. The assembly of a radial glial scaffold is a key step during cortical migration; this study demonstrates that Cas adaptor proteins act downstream of Dystroglycan and b1-Integrin during the establishment of this glial scaffold to regulate cortical lamination.
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影响因子：
16.2
作者：
Cadwell, Cathryn R.;Bhaduri, Aparna;Mostajo-Radji, Mohammed A.;Keefe, Matthew G.;Nowakowski, Tomasz J.
通讯作者：
Nowakowski, Tomasz J.
DOI：
10.1016/j.crmeth.2022.100276
发表时间：
2022-08-22
期刊：
Cell reports methods
影响因子：
--
作者：
通讯作者：
--
影响因子：
1.7
作者：
CAVINESS, VS;TAKAHASHI, T
通讯作者：
TAKAHASHI, T
DOI：
10.1073/pnas.1002285107
发表时间：
2010-07-20
影响因子：
11.1
作者：
Bedogni, Francesco;Hodge, Rebecca D.;Hevner, Robert F.
通讯作者：
Hevner, Robert F.
影响因子：
3.7
作者：
DELRIO, JA;MARTINEZ, A;SORIANO, E
通讯作者：
SORIANO, E