Baltaci Oguzhan, Pedersen Mikael Egebjerg, Sherry Tessa, Handley Ava, Snieckute Goda, Cao Wei, Haas Matilda, Archer Stuart, Pocock Roger
Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC 3800, Australia.
Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, Denmark.
iScience. 2022 Jan 18;25(2):103791. doi: 10.1016/j.isci.2022.103791. eCollection 2022 Feb 18.
Coordinated expression of cell adhesion and signaling molecules is crucial for brain development. Here, we report that the transforming growth factor β (TGF-β) type I receptor SMA-6 (small-6) acts independently of its cognate TGF-β type II receptor DAF-4 (dauer formation-defective-4) to control neuronal guidance. SMA-6 directs neuronal development from the hypodermis through interactions with three, orphan, TGF-β ligands. Intracellular signaling downstream of SMA-6 limits expression of NLR-1, an essential Neurexin-like cell adhesion receptor, to enable neuronal guidance. Together, our data identify an atypical TGF-β-mediated regulatory mechanism to ensure correct neuronal development.
细胞黏附分子和信号分子的协同表达对大脑发育至关重要。在此，我们报告转化生长因子β（TGF-β）I型受体SMA-6（小6）独立于其同源的TGF-β II型受体DAF-4（ dauer形成缺陷-4）发挥作用，以控制神经元导向。SMA-6通过与三种孤儿TGF-β配体相互作用，指导皮下组织的神经元发育。SMA-6下游的细胞内信号传导限制了NLR-1（一种必需的类神经连接蛋白细胞黏附受体）的表达，以实现神经元导向。总之，我们的数据确定了一种非典型的TGF-β介导的调节机制，以确保神经元的正确发育。
