Department of Biology, Texas Woman's University, Denton, TX 76204-5799.
Waksman Institute of Microbiology, Rutgers University, Piscataway, NJ 08854-8020.
Mol Biol Cell. 2019 Dec 15;30(26):3151-3160. doi: 10.1091/mbc.E19-09-0500. Epub 2019 Nov 6.
Bone morphogenetic protein (BMP) signaling pathways control many developmental and homeostatic processes, including cell size and extracellular matrix remodeling. An understanding of how this pathway itself is controlled remains incomplete. To identify novel regulators of BMP signaling, we performed a forward genetic screen in for genes involved in body size regulation, a trait under the control of BMP member DBL-1. We isolated mutations that suppress the long phenotype of , a gene that encodes a negative regulator that sequesters DBL-1. This screen was effective because we isolated alleles of several core components of the DBL-1 pathway, demonstrating the efficacy of the screen. We found additional alleles of previously identified but uncloned body size genes. Our screen also identified widespread involvement of extracellular matrix proteins in DBL-1 regulation of body size. We characterized interactions between the DBL-1 pathway and extracellular matrix and other genes that affect body morphology. We discovered that loss of some of these genes affects the DBL-1 pathway, and we provide evidence that DBL-1 signaling affects many molecular and cellular processes associated with body size. We propose a model in which multiple body size factors are controlled by signaling through the DBL-1 pathway and by DBL-1-independent processes.
骨形态发生蛋白(BMP)信号通路控制着许多发育和动态平衡过程,包括细胞大小和细胞外基质重塑。人们对该通路本身如何受到调控的认识仍不完整。为了鉴定 BMP 信号的新调控因子,我们在 中进行了正向遗传筛选,以寻找参与体型调控的基因,这是 BMP 成员 DBL-1 控制的一个特征。我们分离出了抑制 长表型的突变,该基因编码一种负调控因子,可隔离 DBL-1。该筛选是有效的,因为我们分离出了 DBL-1 通路的几个核心成分的等位基因,这证明了筛选的效果。我们还发现了以前鉴定但未克隆的体型基因的其他等位基因。我们的筛选还表明细胞外基质蛋白广泛参与 DBL-1 对体型的调控。我们研究了 DBL-1 通路与细胞外基质以及其他影响身体形态的基因之间的相互作用。我们发现,这些基因中的一些缺失会影响 DBL-1 通路,并且我们提供了证据表明 DBL-1 信号会影响与体型相关的许多分子和细胞过程。我们提出了一个模型,其中多个体型因子通过 DBL-1 通路的信号传递和 DBL-1 独立的过程受到调控。