Xie Linjun, Ma Roger C, Kocha Katrinka M, Méndez-Olivos Emilio E, Huang Peng
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Development. 2025 Jun 15;152(12). doi: 10.1242/dev.204321. Epub 2025 Jun 23.
The sclerotome is an embryonic structure that gives rise to various supportive tissues, including the axial skeleton and connective tissues. Despite its significance, the mechanisms underlying sclerotome induction and diversification during embryonic development remain poorly understood. Sclerotome progenitors exhibit transient bmp4 expression and an active response to BMP signaling. Using BMP gain- and loss-of-function tools, we demonstrate that BMP signaling is both necessary and sufficient for sclerotome induction. Furthermore, through mosaic expression of a dominant-negative tool, we show that BMP signaling induces sclerotome fate in a cell-autonomous manner. Interestingly, different populations of sclerotome-derived cells have distinct BMP signaling requirements. Sclerotome-derived notochord-associated cells in the trunk lack any BMP response, and sustained BMP signaling inhibits their differentiation into tenocytes. By contrast, sclerotome-derived fin mesenchymal cells in the fin fold require high levels of BMP signaling for proper morphogenesis. Our findings suggest that dynamic regulation of BMP signaling is crucial for the induction of the sclerotome and the subsequent diversification of sclerotome-derived lineages in zebrafish.
体节是一种胚胎结构，可产生各种支持组织，包括中轴骨骼和结缔组织。尽管其具有重要意义，但胚胎发育过程中体节诱导和分化的潜在机制仍知之甚少。体节祖细胞表现出短暂的bmp4表达以及对BMP信号的活跃反应。使用BMP功能获得和功能丧失工具，我们证明BMP信号对于体节诱导既是必要的也是充分的。此外，通过显性负性工具的镶嵌表达，我们表明BMP信号以细胞自主方式诱导体节命运。有趣的是，不同群体的体节衍生细胞具有不同的BMP信号需求。躯干中体节衍生的脊索相关细胞缺乏任何BMP反应，持续的BMP信号抑制它们分化为肌腱细胞。相比之下，鳍褶中体节衍生的鳍间充质细胞需要高水平的BMP信号来进行正常的形态发生。我们的研究结果表明，BMP信号的动态调节对于斑马鱼体节的诱导以及随后体节衍生谱系的多样化至关重要。
