Wang M, Sternberg P W
Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, California, 91125, USA.
Dev Biol. 1999 Aug 1;212(1):12-24. doi: 10.1006/dbio.1999.9357.
Multipotent Caenorhabditis elegans vulval precursor cells (VPCs) choose among three fates (1 degrees, 2 degrees, and 3 degrees ) in response to two intercellular signals: the EGF family growth factor LIN-3 induces 1 degrees fates at high levels and 2 degrees fates at low levels; and a signal via the receptor LIN-12 induces 2 degrees fates. If the level of LIN-3 signal is reduced by a lin-3 hypomorphic mutation, the daughters of the VPC closest to the anchor cell (AC), P6.p, are induced by the AC. By expressing LIN-3 as a function of time in LIN-3-deficient animals, we find that both VPCs and the daughters of VPCs are competent to respond to LIN-3, and VPC daughters lose competence after fusing with the hypodermis. We also demonstrate that the daughters of VPCs specified to be 2 degrees can respond to LIN-3, indicating that 2 degrees VPCs are not irreversibly committed. We propose that maintenance of VPC competence after the first cell cycle and the prioritization of the 1 degrees fate help ensure that P6.p will become 1 degrees. This mechanism of competence regulation might have been maintained from ancestral nematode species that used induction both before and after VPC division and serves to maximize the probability that a functional vulva is formed.
多能性的秀丽隐杆线虫外阴前体细胞(VPCs)会根据两种细胞间信号在三种命运(1°、2°和3°)中做出选择:表皮生长因子(EGF)家族生长因子LIN-3在高水平时诱导1°命运,在低水平时诱导2°命运;通过受体LIN-12传递的信号诱导2°命运。如果通过lin-3次等位基因突变降低LIN-3信号水平,最靠近锚定细胞(AC)的VPC的子代细胞,即P6.p,会被AC诱导。通过在LIN-3缺陷型动物中根据时间表达LIN-3,我们发现VPC及其子代细胞都有能力对LIN-3做出反应,并且VPC子代细胞在与皮下组织融合后失去反应能力。我们还证明,被指定为2°命运的VPC子代细胞能够对LIN-3做出反应,这表明2°命运的VPC并非不可逆转地被决定。我们提出,在第一个细胞周期后维持VPC的反应能力以及优先选择1°命运有助于确保P6.p成为1°命运。这种反应能力调节机制可能是从在VPC分裂前后都利用诱导作用的祖先线虫物种那里保留下来的,并且有助于最大化形成功能性外阴的概率。