期刊
DEVELOPMENT
卷 147, 期 11, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.190488
关键词
IGF; Angiocrine; Craniofacial; Cartilage; Blood vessel; Mouse
资金
- National Health and Medical Research Council (NHMRC) [APP1144008]
- Royal Adelaide Hospital Research Fund Mary Overton Fellowship
- National Heart Foundation of Australia Future Leader Fellowship
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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