Plpp3 regulates craniofacial morphogenesis but is dispensable for establishing the midbrain-hindbrain boundary

Phospholipid Phosphatase 3 (PLPP3), an integral membrane enzyme, is essential for embryonic development. It plays a critical role in lipid metabolism and in regulating the cell signaling of several bioactive lipid mediators. One of these lipids, LPA, has been suggested to participate in establishing the midbrain-hindbrain boundary (MHB) and in cranial neural tube closure in mice, and in neural crest migration in frogs. To uncover PLPP3's role in these processes, we studied the effects of global and conditional Plpp3 inactivation in Wnt1::Cre2-expressing domains. We show that Plpp3 expression is dispensable for establishing the MHB, although our data support the involvement of LPA-mediated signaling in regulating Fgf8 expression during anterior embryo development. Its deficiency in neural crest cells yields craniofacial dysmorphology and neonatal lethality due to cardiac failure. Craniofacial defects include a reduced mid frontonasal process, hypotelorism, and an anterior shift of the coronal suture position, driven by localized cell death between E10.5 and E11.5. Our work reveals novel functions of PLPP3 in regulating craniofacial development and coronal suture positioning.