論文 - 詳細
| RRC ID | 87166 |
|---|---|
| 著者 | Makhlouf A, Wang A, Sato N, Rosa VS, Shahbazi MN. |
| タイトル | Integrin signaling in pluripotent cells acts as a gatekeeper of mouse germline entry. |
| ジャーナル | Sci Adv |
| Abstract |
Primordial germ cells (PGCs) are the precursors of gametes and the sole mechanism by which animals transmit genetic information across generations. In the mouse embryo, the transcriptional and epigenetic regulation of PGC specification has been extensively characterized. However, the initial event that triggers the soma-germline segregation remains poorly understood. Here, we uncover a critical role for the basement membrane in regulating germline entry. We show that PGCs arise in a region of the mouse embryo that lacks contact with the basement membrane, and the addition of exogenous extracellular matrix (ECM) inhibits both PGC and PGC-like cell (PGCLC) specification in mouse embryos and stem cell models, respectively. Mechanistically, we demonstrate that the engagement of β1 integrin with laminin blocks PGCLC specification by preventing the Wnt signaling-dependent down-regulation of the PGC transcriptional repressor, Otx2. In this way, the physical segregation of cells away from the basement membrane acts as a morphogenetic fate switch that controls the soma-germline bifurcation. |
| 巻・号 | 10(36) |
| ページ | eadk2252 |
| 公開日 | 2024-9-6 |
| DOI | 10.1126/sciadv.adk2252 |
| PMID | 39231227 |
| PMC | PMC11373592 |
| MeSH | Animals Basement Membrane / metabolism Cell Differentiation Embryo, Mammalian / cytology Embryo, Mammalian / metabolism Extracellular Matrix / metabolism Gene Expression Regulation, Developmental Germ Cells* / cytology Germ Cells* / metabolism Integrin beta1 / genetics Integrin beta1 / metabolism Integrins / genetics Integrins / metabolism Laminin / metabolism Mice Otx Transcription Factors / genetics Otx Transcription Factors / metabolism Pluripotent Stem Cells* / cytology Pluripotent Stem Cells* / metabolism Signal Transduction Wnt Signaling Pathway |
| IF | 13.117 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 45 |
| 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 | |
| 実験動物マウス | RBRC05384 |