Reference - Detail
| RRC ID | 87166 |
|---|---|
| Author | Makhlouf A, Wang A, Sato N, Rosa VS, Shahbazi MN. |
| Title | Integrin signaling in pluripotent cells acts as a gatekeeper of mouse germline entry. |
| Journal | 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. |
| Volume | 10(36) |
| Pages | eadk2252 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 45 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC05384 |