Requirement for the Ip(A1) lysophosphatidic acid receptor gene in normal suckling behavior

Although extracellular application of lysophosphatidic acid (LPA) has been extensively documented to produce a variety of cellular responses through a family of specific G protein-coupled receptors, the in vivo organismal rol e of LPA signaling remains largely unknown. The first identified LPA recept or gene, I-pA1/vzg-1/ edg-2, was previously shown to have remarkably enrich ed embryonic expression in the cerebral cortex and dorsal olfactory bulb an d postnatal expression in myelinating glia including Schwann cells. Here, w e show that targeted deletion of I-pA1 results in approximately 50% neonata l lethality, impaired suckling in neonatal pups, and loss of LPA responsivi ty in embryonic cerebral cortical neuroblasts with survivors showing reduce d size, craniofacial dysmorphism, and increased apoptosis in sciatic nerve Schwann cells. The suckling defect was responsible for the death among I-pA 1(-/-) neonates and the stunted growth of survivors. Impaired suckling beha vior was attributable to defective olfaction, which is likely related to de velopmental abnormalities in olfactory bulb and/or cerebral cortex. Our res ults provide evidence that endogenous lysophospholipid signaling requires a n Ip receptor gene and indicate that LPA signaling through the LPA1 recepto r is required for normal development of an inborn, neonatal behavior.