Chen Ning, Greenwald Iva
Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, College of Physicians and Surgeons, 701 West 168th Street, Room 720, New York, NY 10032, USA.
Dev Cell. 2004 Feb;6(2):183-92. doi: 10.1016/s1534-5807(04)00021-8.
The vulval precursor cells (VPCs) are spatially patterned by a LET-23/EGF receptor-mediated inductive signal and a LIN-12/Notch-mediated lateral signal. The lateral signal has eluded identification, so the mechanism by which lateral signaling is activated has not been known. Here, we computationally identify ten genes that encode potential ligands for LIN-12, and show that three of these genes, apx-1, dsl-1, and lag-2, are functionally redundant components of the lateral signal. We also show that transcription of all three genes is initiated or upregulated in VPCs in response to inductive signaling, suggesting that direct transcriptional control of the lateral signal by the inductive signal is part of the mechanism by which these cell signaling events are coordinated. In addition, we show that DSL-1, which lacks a predicted transmembrane domain, is a natural secreted ligand and can substitute for the transmembrane ligand LAG-2 in different functional assays.
外阴前体细胞（VPCs）通过LET-23/表皮生长因子受体介导的诱导信号和LIN-12/Notch介导的侧向信号在空间上形成模式。侧向信号一直难以鉴定，因此侧向信号激活的机制尚不清楚。在这里，我们通过计算鉴定出十个编码LIN-12潜在配体的基因，并表明其中三个基因apx-1、dsl-1和lag-2是侧向信号的功能冗余成分。我们还表明，这三个基因的转录在VPCs中响应诱导信号而启动或上调，这表明诱导信号对侧向信号的直接转录控制是这些细胞信号事件协调机制的一部分。此外，我们表明，缺乏预测跨膜结构域的DSL-1是一种天然分泌配体，并且在不同的功能测定中可以替代跨膜配体LAG-2。
