Adipose tissue is distributed in depots throughout the body with specialized roles in energy storage and thermogenesis. PDGFRα is a marker of adipocyte precursors, and increased PDGFRα activity causes adipose tissue fibrosis in adult mice. However, the function of PDGFRα during adipose tissue organogenesis is unknown. Here, by analyzing mice with juxtamembrane or kinase domain point mutations that increase PDGFRα activity (V561D or D842V), we found that PDGFRα activation inhibits embryonic white adipose tissue organogenesis in a tissue-autonomous manner. By lineage tracing analysis, we also found that collagen-expressing precursor fibroblasts differentiate into white adipocytes in the embryo. PDGFRα inhibited the formation of adipocytes from these precursors while favoring the formation of stromal fibroblasts. This imbalance between adipocytes and stromal cells was accompanied by overexpression of the cell fate regulator Zfp521. PDGFRα activation also inhibited the formation of juvenile beige adipocytes in the inguinal fat pad. Our data highlight the importance of balancing stromal versus adipogenic cell expansion during white adipose tissue development, with PDGFRα activity coordinating this crucial process in the embryo.
The authors declare no competing or financial interests.
C.S. performed all experiments. W.L.B. assisted with lineage tracing experiments. C.S. and L.E.O. designed the experiments, interpreted the data and wrote the manuscript.
This research was supported by grants from the National Institutes of Health (5P20GM103636), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (1R01AR070235) and the Oklahoma Center for Adult Stem Cell Research (OCASCR) to L.E.O. C.S. was supported by a predoctoral fellowship from the American Heart Association. L.E.O. is a Pew Scholar in Biomedical Research, and this work was supported in part by the Pew Charitable Trusts. Deposited in PMC for release after 12 months.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.135962.supplemental
- Received January 30, 2016.
- Accepted November 9, 2016.