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Publication : Vessel-derived angiocrine IGF1 promotes Meckel's cartilage proliferation to drive jaw growth during embryogenesis.

First Author  Marchant C Year  2020
Journal  Development Volume  147
Issue  11 PubMed ID  32439763
Mgi Jnum  J:290858 Mgi Id  MGI:6437711
Doi  10.1242/dev.190488 Citation  Marchant C, et al. (2020) Vessel-derived angiocrine IGF1 promotes Meckel's cartilage proliferation to drive jaw growth during embryogenesis. Development 147(11):dev190488
abstractText  Craniofacial development is a complex morphogenic process that requires highly orchestrated interactions between multiple cell types. Blood vessel-derived angiocrine factors are known to promote proliferation of chondrocytes in Meckel's cartilage to drive jaw outgrowth, however the specific factors controlling this process remain unknown. Here, we use in vitro and ex vivo cell and tissue culture, as well as genetic mouse models, to identify IGF1 as a novel angiocrine factor directing Meckel's cartilage growth during embryonic development. We show that IGF1 is secreted by blood vessels and that deficient IGF1 signalling underlies mandibular hypoplasia in Wnt1-Cre; Vegfa(fl/fl) mice that exhibit vascular and associated jaw defects. Furthermore, conditional removal of IGF1 from blood vessels causes craniofacial defects including a shortened mandible, and reduced proliferation of Meckel's cartilage chondrocytes. This demonstrates a crucial angiocrine role for IGF1 during craniofacial cartilage growth, and identifies IGF1 as a putative therapeutic for jaw and/or cartilage growth disorders.
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