δ-Protocadherins regulate neural progenitor cell division by antagonizing Ryk and Wnt/β-catenin signaling.
δ-Protocadherins regulate neural progenitor cell division by antagonizing Ryk and Wnt/β-catenin signaling.
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δ-原钙粘蛋白通过拮抗Ryk和Wnt/β-catenin信号通路调节神经前体细胞分裂。
DOI：
10.1016/j.isci.2021.102932
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发表时间：
2021-08-20
期刊：
影响因子：
5.8
通讯作者：
Jontes JD
中科院分区：
文献类型：
--
作者：
Biswas S;Emond MR;Chenoweth KP;Jontes JD
神经祖细胞的分裂提供了神经系统在发育过程中形成的细胞基质。亲同质细胞粘附分子δ-原钙粘蛋白家族对脊椎动物神经系统的发育至关重要，并与一系列神经发育障碍有关。我们发现，任何六种个体δ-原钙粘蛋白的病变都会增加后脑神经祖细胞的细胞分裂。这种增加是由于Wnt/β-catenin信号的错误调节，因为该途径在δ-原钙粘蛋白突变体中上调，抑制该途径可阻断细胞分裂的增加。此外，δ-原钙粘蛋白可以与Wnt受体Ryk复合物存在，Ryk是原钙粘蛋白突变体增殖增加所必需的。因此，δ-原钙粘蛋白是Wnt/β-catenin信号传导的新型调节剂，可能通过定义神经祖细胞身份的分子密码和差异调节其增殖来控制神经回路的发育。δ-pcdhs个体缺失导致斑马鱼后脑增殖升高δ-pcdhs突变体显示Wnt/β-catenin信号通路升高抑制Wnt/β-catenin信号通路抑制δ-pcdh突变体增殖升高Wnt受体Ryk是δ-pcdh突变体增殖升高所必需的；细胞生物学;发育生物学
The division of neural progenitor cells provides the cellular substrate from which the nervous system is sculpted during development. The δ-protocadherin family of homophilic cell adhesion molecules is essential for the development of the vertebrate nervous system and is implicated in an array of neurodevelopmental disorders. We show that lesions in any of six, individual δ-protocadherins increases cell divisions of neural progenitors in the hindbrain. This increase is due to mis-regulation of Wnt/β-catenin signaling, as this pathway is upregulated in δ-protocadherin mutants and inhibition of this pathway blocks the increase in cell division. Furthermore, the δ-protocadherins can be present in complex with the Wnt receptor Ryk, and Ryk is required for the increased proliferation in protocadherin mutants. Thus, δ-protocadherins are novel regulators of Wnt/β-catenin signaling that may control the development of neural circuits by defining a molecular code for the identity of neural progenitor cells and differentially regulating their proliferation. Loss of individual δ-pcdhs leads to elevated proliferation in the zebrafish hindbrain Zebrafish mutants lacking δ-pcdhs show elevated Wnt/β-catenin signaling Inhibiting Wnt/β-catenin signaling blocks elevated proliferation in δ-pcdh mutants The Wnt receptor Ryk is required for the elevated proliferation in δ-pcdh mutants Molecular neuroscience; Cell biology; Developmental biology
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影响因子：
64.8
作者：
Bonkowsky, JL;Yoshikawa, S;Thomas, JB
通讯作者：
Thomas, JB
DOI：
10.1083/jcb.201107021
发表时间：
2011-09-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Berndt JD;Aoyagi A;Yang P;Anastas JN;Tang L;Moon RT
通讯作者：
Moon RT
DOI：
10.1083/jcb.201507108
发表时间：
2015-11-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cooper SR;Emond MR;Duy PQ;Liebau BG;Wolman MA;Jontes JD
通讯作者：
Jontes JD
影响因子：
3.3
作者：
Biswas S;Emond MR;Duy PQ;Hao le T;Beattie CE;Jontes JD
通讯作者：
Jontes JD
影响因子：
6.1
作者：
Homan, Claire C.;Pederson, Stephen;Gecz, Jozef
通讯作者：
Gecz, Jozef