Gorrepati Lakshmi, Eisenmann David M
Carnegie Institution for Science; Department of Embryology ; Baltimore, MD USA.
Department of Biological Sciences; University of Maryland Baltimore County ; Baltimore, MD USA.
Worm. 2015 Jan 27;4(1):e996419. doi: 10.1080/23723556.2014.996419. eCollection 2015 Jan-Mar.
In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further. Wnt signaling pathway is known to regulate the asymmetry of these divisions and maintain the progenitor cell fate in one daughter, but how activation of the Wnt pathway accomplished this was unknown. We describe here our recent work that identified the GATA transcription factor EGL-18 as a downstream target of Wnt signaling necessary for maintenance of a progenitor population of larval seam cells. EGL-18 was previously shown to act in the initial specification of the seam cells in the embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an embryonic fate specification factor to be reutilized later in life downstream of a different regulator (Wnt signaling) to maintain a progenitor cell population. These results support the use of seam cell development in C. elegans as a simple model system for studying stem and progenitor cell biology.
在多细胞动物中,发育中和成体组织中的干细胞可进行不对称分裂,产生一个分化的子代细胞和一个保留祖细胞命运的子代细胞。尽管寿命短暂的线虫秀丽隐杆线虫不具备成体体细胞干细胞,但外侧皮下的接缝细胞表现出类似的行为:它们在每个幼虫阶段分裂一次,产生一个采取非分裂分化命运的前侧子代细胞和一个保留接缝细胞命运并具有进一步分裂能力的后侧子代细胞。已知Wnt信号通路可调节这些分裂的不对称性,并在一个子代细胞中维持祖细胞命运,但Wnt通路的激活是如何实现这一点的尚不清楚。我们在此描述了我们最近的工作,该工作确定了GATA转录因子EGL-18是维持幼虫接缝细胞祖细胞群体所必需的Wnt信号的下游靶点。EGL-18先前已被证明在胚胎接缝细胞的初始特化中起作用。因此,获得一个对Wnt有反应的顺式调节模块,使得一个胚胎命运特化因子能够在生命后期在不同调节因子(Wnt信号)的下游被重新利用,以维持祖细胞群体。这些结果支持将秀丽隐杆线虫中的接缝细胞发育用作研究干细胞和祖细胞生物学的简单模型系统。