当前位置: X-MOL 学术Science › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain
Science ( IF 56.9 ) Pub Date : 2024-05-02 , DOI: 10.1126/science.ade6970
Gareth T. Powell 1, 2 , Ana Faro 1 , Yuguang Zhao 3 , Heather Stickney 1, 4, 5 , Laura Novellasdemunt 6, 7 , Pedro Henriques 1 , Gaia Gestri 1 , Esther Redhouse White 1 , Jingshan Ren 3 , Weixian Lu 3 , Rodrigo M. Young 1, 8, 9 , Thomas A. Hawkins 1 , Florencia Cavodeassi 1, 10 , Quenten Schwarz 8 , Elena Dreosti 1 , David W. Raible 4 , Vivian S. W. Li 6 , Gavin J. Wright 2, 11 , E. Yvonne Jones 3 , Stephen W. Wilson 1
Affiliation  

Neurons on the left and right sides of the nervous system often show asymmetric properties, but how such differences arise is poorly understood. Genetic screening in zebrafish revealed that loss of function of the transmembrane protein Cachd1 resulted in right-sided habenula neurons adopting left-sided identity. Cachd1 is expressed in neuronal progenitors, functions downstream of asymmetric environmental signals, and influences timing of the normally asymmetric patterns of neurogenesis. Biochemical and structural analyses demonstrated that Cachd1 can bind simultaneously to Lrp6 and Frizzled family Wnt co-receptors. Consistent with this, lrp6 mutant zebrafish lose asymmetry in the habenulae, and epistasis experiments support a role for Cachd1 in modulating Wnt pathway activity in the brain. These studies identify Cachd1 as a conserved Wnt receptor–interacting protein that regulates lateralized neuronal identity in the zebrafish brain.

中文翻译:

Cachd1 与 Wnt 受体相互作用并调节斑马鱼大脑中的神经元不对称性

神经系统左右两侧的神经元通常表现出不对称特性,但人们对这种差异是如何产生的知之甚少。对斑马鱼的基因筛查显示,跨膜蛋白 Cachd1 功能丧失导致右侧缰核神经元采用左侧身份。 Cachd1 在神经元祖细胞中表达,在不对称环境信号的下游发挥作用,并影响神经发生的正常不对称模式的时间。生化和结构分析表明,Cachd1 可以同时与 Lrp6 和 Frizzled 家族 Wnt 共受体结合。与此相一致的是,lrp6突变斑马鱼失去了缰核的不对称性,上位性实验支持 Cachd1 在调节大脑中 Wnt 通路活性中的作用。这些研究将 Cachd1 确定为一种保守的 Wnt 受体相互作用蛋白,可调节斑马鱼大脑中的侧化神经元身份。
更新日期:2024-05-02
down
wechat
bug