論文 - 詳細
| RRC ID | 84151 |
|---|---|
| 著者 | Fakieh RA, Reiner DJ. |
| タイトル | RAP-2 and CNH-MAP4 Kinase MIG-15 confer resistance in bystander epithelium to cell-fate transformation by excess Ras or Notch activity. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Induction of cell fates by growth factors impacts many facets of developmental biology and disease. LIN-3/EGF induces the equipotent vulval precursor cells (VPCs) in Caenorhabditis elegans to assume the 3˚-3˚-2˚-1˚-2˚-3˚ pattern of cell fates. 1˚ and 2˚ cells become specialized epithelia and undergo stereotyped series of cell divisions to form the vulva. Conversely, 3˚ cells are relatively quiescent and nonspecialized; they divide once and fuse with the surrounding epithelium. 3˚ cells have thus been characterized as passive, uninduced, or ground state. Based on our previous studies, we hypothesized that a 3˚-promoting program would confer resistance to cell fate-transformation by inappropriately activated 1˚ and 2˚ fate-promoting LET-60/Ras and LIN-12/Notch, respectively. Deficient MIG-15/CNH-MAP4 Kinase meets the expectations of genetic interactions for a 3˚-promoting protein. Moreover, endogenous MIG-15 is required for expression of a fluorescent biomarker of 3˚ cell fate, is expressed in VPCs, and functions cell autonomously in VPCs. The Ras family small GTPase RAP-2, orthologs of which activate orthologs of MIG-15 in other systems, emulates these functions of MIG-15. However, gain of RAP-2 function has no effect on patterning, suggesting its activity is constitutive in VPCs. The 3˚ biomarker is expressed independently of the AC, raising questions about the cellular origin of 3˚-promoting activity. Activated LET-60/Ras and LIN-12/Notch repress expression of the 3˚ biomarker, suggesting that the 3˚-promoting program is both antagonized by as well as antagonizes 1˚- and 2˚- promoting programs. This study provides insight into developmental properties of cells historically considered to be nonresponding to growth factor signals. |
| 巻・号 | 122(1) |
| ページ | e2414321121 |
| 公開日 | 2025-1-7 |
| DOI | 10.1073/pnas.2414321121 |
| PMID | 39739816 |
| PMC | PMC11725784 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cell Differentiation Epithelium / metabolism Female Receptors, Notch* / genetics Receptors, Notch* / metabolism Signal Transduction Vulva* / cytology Vulva* / metabolism ras Proteins* / genetics ras Proteins* / metabolism |
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm5840 |