Chidiac Rony, Angers Stephane
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Curr Top Dev Biol. 2023;153:121-143. doi: 10.1016/bs.ctdb.2023.01.005. Epub 2023 Feb 20.
During embryo development, cell proliferation, cell fate specification and tissue patterning are coordinated and tightly regulated by a handful of evolutionarily conserved signaling pathways activated by secreted growth factor families including fibroblast growth factor (FGF), Nodal/bone morphogenetic protein (BMP), Hedgehog and Wnt. The spatial and temporal activation of these signaling pathways elicit context-specific cellular responses that ultimately shape the different tissues of the embryo. Extensive efforts have been dedicated to identifying the molecular mechanisms underlying these signaling pathways during embryo development, adult tissue homeostasis and regeneration. In this review, we first describe the role of the Wnt/β-catenin signaling pathway during early embryo development, axis specification and cell differentiation as a prelude to highlight how this knowledge is being leveraged to manipulate Wnt/β-catenin signaling activity with small molecules and biologics for the directed differentiation of pluripotent stem cells into various cell lineages that are physiologically relevant for stem cell therapy and regenerative medicine.
在胚胎发育过程中，细胞增殖、细胞命运特化和组织模式形成由少数进化保守的信号通路协调并严格调控，这些信号通路由包括成纤维细胞生长因子（FGF）、Nodal/骨形态发生蛋白（BMP）、刺猬因子和Wnt在内的分泌型生长因子家族激活。这些信号通路的时空激活引发特定背景下的细胞反应，最终塑造胚胎的不同组织。人们付出了巨大努力来确定这些信号通路在胚胎发育、成体组织稳态和再生过程中的分子机制。在这篇综述中，我们首先描述Wnt/β-连环蛋白信号通路在早期胚胎发育、轴特化和细胞分化过程中的作用，以此作为前奏来突出如何利用这些知识，通过小分子和生物制剂来操纵Wnt/β-连环蛋白信号活性，从而将多能干细胞定向分化为与干细胞治疗和再生医学生理相关的各种细胞谱系。
