Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling
| Autor: | Aimée Zuniga, Fabiana Gullotta, Erkan Ünal, Robert Ivanek, Robert Reinhardt, Gretel Nusspaumer, Rolf Zeller |
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| Přispěvatelé: | University of Basel, Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen, German Research Foundation |
| Rok vydání: | 2019 |
| Předmět: |
Limb Buds
Mesenchyme Mouse limb bud Biology Fibroblast growth factor Transcriptomes Mesoderm 03 medical and health sciences Limb bud Mice 0302 clinical medicine medicine Animals Hedgehog Proteins Progenitor cell Molecular Biology 030304 developmental biology 0303 health sciences Mesenchymal stem cell Gene Expression Regulation Developmental Signaling Cell biology Fibroblast Growth Factors Cell sorting medicine.anatomical_structure Intercellular Signaling Peptides and Proteins Mesenchymal progenitors Forelimb Gremlin (protein) Transcriptome Chondrogenesis 030217 neurology & neurosurgery Developmental Biology Morphogen Signal Transduction Research Article |
| Zdroj: | Development (Cambridge, England) Digital.CSIC. Repositorio Institucional del CSIC instname Development |
| Popis: | The key molecular interactions governing vertebrate limb bud development are a paradigm for studying the mechanisms controlling progenitor cell proliferation and specification during vertebrate organogenesis. However, little is known about the cellular heterogeneity of the mesenchymal progenitors in early limb buds that ultimately contribute to the chondrogenic condensations prefiguring the skeleton. We combined flow cytometric and transcriptome analyses to identify the molecular signatures of several distinct mesenchymal progenitor cell populations present in early mouse forelimb buds. In particular, jagged 1 (JAG1)-positive cells located in the posterior-distal mesenchyme were identified as the most immature limb bud mesenchymal progenitors (LMPs), which crucially depend on SHH and FGF signaling in culture. The analysis of gremlin 1 (Grem1)-deficient forelimb buds showed that JAG1-expressing LMPs are protected from apoptosis by GREM1-mediated BMP antagonism. At the same stage, the osteo-chondrogenic progenitors (OCPs) located in the core mesenchyme are already actively responding to BMP signaling. This analysis sheds light on the cellular heterogeneity of the early mouse limb bud mesenchyme and on the distinct response of LMPs and OCPs to morphogen signaling. Summary: Cell sorting identifies limb bud mesenchymal progenitors (LMPs) with distinct molecular signatures and differential dependence on morphogen signaling. Specifically, two immature LMP populations with strong chondrogenic differentiation potential are identified. |
| Databáze: | OpenAIRE |
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