Platelet Derived Growth factor Receptor α (PDGFRα) in Liver Development

Abstract

PDGFRα signaling is critical and indispensable during development. Global inactivation of this receptor has been shown to be embryonic lethal. The critical role of this receptor during development has been shown in certain organs including, lung and brain. Liver development is a complex and temporal process, which entails a balanced regulation of proliferation and differentiation of the bipotential stem cells (hepatoblasts) of the liver. Recently, robust PDGFRα expression was identified as early as embryonic day 11 during early liver development albeit with a gradual decrease until birth. Additional PDGF‐CC, a ligand for PDGFRα was observed during early and PDGF‐AA at late stages of hepatic development, while PDGF‐BB was expressed at all times. Using phospho‐specific antibodies to PDGFRα, temporal phosphorylation events were identified only during early hepatic development indicating downstream activation of specific pathways. PDGFRβ was also expressed during early liver development. However, double immunofluorescence studies identified hepatocyte specific hepatic nuclear factor 4 alpha (HNF4α) to colocalize with PDGFRα and not PDGFRβ. Based on ongoing proliferation, survival and differentiation of hepatoblasts and hepatocytes at early stages of hepatic development and concomitant PDGFRα signaling at the same stages, we conclude that PDGFRα may be an important mediator of these critical biological events in hepatic development. Funded by CATER fellowship (NIH T32 EB001026‐05) to PA; 1R01DK62277 and 1R01CA124414 to SPM