Division of Biology, Kansas State University, Manhattan, KS 66506, USA.
Dev Biol. 2013 Mar 15;375(2):117-27. doi: 10.1016/j.ydbio.2012.12.002. Epub 2012 Dec 12.
The tailbud is a population of stem cells in the posterior embryonic tail. During zebrafish development, these stem cells give rise to the main structures of the embryo's posterior body, including the tail somites. Progenitor cells reside in the tailbud for variable amounts of time before they exit and begin to differentiate. There must be a careful balance between cells that leave the tailbud and cells that are held back in order to give rise to later somites. However, this meticulous process is not well understood. A gene that has shed some light on this area is the t-box transcription factor spadetail (spt). When spt is mutated, embryos develop an enlarged tailbud and are only able to form roughly half of their somites. This phenotype is due to the fact that some of the somitic precursors are not able to leave the tailbud or differentiate. Another factor involved in tail morphogenesis is the Bone Morphogenetic Protein (BMP) pathway. BMPs are important for many processes during early development, including cell migration. Chordino (chd) is a secreted protein that inhibits BMP signaling. BMPs are upregulated in chd mutants, however, these mutants are able to form organized somites. In embryos where chd and spt are mutated, somites are completely absent. These double mutants also develop a large tailbud due to the accumulation of progenitor cells that are never able to leave or differentiate. To study the dynamics of cells in the tailbud and their role in somite formation, we have analyzed the genetic factors and pathway interactions involved, conducted transplant experiments to look at behavior of mutant cells in different genetic backgrounds, and used time lapse microscopy to characterize cell movements and behavior in wild type and mutant tailbuds. These data suggest that spt expression and BMP inhibition are both required for somitic precursors to exit the tailbud. They also elucidate that chd;spt tailbud mesodermal progenitor cells (MPC) behave autonomously and their dynamics within the tailbud are drastically different than WT MPCs.
尾芽是胚胎尾部的一群干细胞。在斑马鱼的发育过程中，这些干细胞会产生胚胎尾部的主要结构，包括尾节。祖细胞在离开并开始分化之前，会在尾芽中停留一段时间。为了产生后面的节段，离开尾芽的细胞和被保留的细胞之间必须保持精细的平衡。然而，这个精细的过程还没有被很好地理解。一个在这个领域提供了一些启示的基因是 T 盒转录因子 spadetail (spt)。当 spt 发生突变时，胚胎会发育出一个增大的尾芽，只能形成大约一半的节段。这种表型是由于一些节段前体不能离开尾芽或分化。另一个参与尾巴形态发生的因素是骨形态发生蛋白 (BMP) 途径。BMPs 在早期发育的许多过程中都很重要，包括细胞迁移。Chordino (chd) 是一种分泌蛋白，它抑制 BMP 信号。然而，在 chd 突变体中 BMPs 被上调，这些突变体能够形成有组织的节段。在 chd 和 spt 都发生突变的胚胎中，节段完全缺失。这些双突变体也由于从未能够离开或分化的祖细胞的积累而发育出一个大的尾芽。为了研究尾芽中的细胞动态及其在节段形成中的作用，我们分析了涉及的遗传因素和途径相互作用，进行了移植实验来观察突变细胞在不同遗传背景下的行为，并使用延时显微镜来描述野生型和突变型尾芽中的细胞运动和行为。这些数据表明，spt 表达和 BMP 抑制都是节段前体离开尾芽所必需的。它们还阐明了 chd;spt 尾芽中胚层祖细胞 (MPC) 是自主行为的，它们在尾芽中的动态与 WT MPC 有很大的不同。
