Requirement for the IpA1 lysophosphatidic acid receptor gene in normal suckling behavior
Requirement for the IpA1 lysophosphatidic acid receptor gene in normal suckling behavior
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DOI：
10.1073/pnas.97.24.13384
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发表时间：
2000-11-21
影响因子：
11.1
通讯作者：
Chun, J
中科院分区：
文献类型：
--
作者：
Contos, JJA;Fukushima, N;Chun, J
虽然细胞外应用溶血磷脂酸（LPA）已被广泛记录，以产生各种细胞反应，通过一个家庭的特定G蛋白偶联受体，在体内生物体的作用LPA信号仍然在很大程度上未知。第一个确定的LPA受体基因，I-pA 1/vzg-1/ edg-2，以前被证明有显着丰富的胚胎表达在大脑皮层和背嗅球和出生后的表达在髓鞘神经胶质细胞，包括雪旺细胞。在这里，我们表明，有针对性的删除I-PA 1的结果在约50%的新生儿死亡率，受损的新生儿幼崽的哺乳，并在胚胎大脑皮层神经母细胞LPA反应性的损失与幸存者表现出减少的大小，颅面畸形，并增加坐骨神经雪旺细胞的凋亡。I-pA 1（-/-）新生儿的死亡和存活儿的生长发育迟缓与哺乳缺陷有关。哺乳行为受损可归因于嗅觉缺陷，这可能与嗅球和/或大脑皮层的发育异常有关。我们的研究结果提供的证据表明，内源性溶血磷脂信号需要一个IP受体基因，并表明通过LPA 1受体的LPA信号是所需的先天性，新生儿行为的正常发展。
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 role of LPA signaling remains largely unknown. The first identified LPA receptor gene, I-pA1/vzg-1/ edg-2, was previously shown to have remarkably enriched embryonic expression in the cerebral cortex and dorsal olfactory bulb and postnatal expression in myelinating glia including Schwann cells. Here, we show that targeted deletion of I-pA1 results in approximately 50% neonatal lethality, impaired suckling in neonatal pups, and loss of LPA responsivity in embryonic cerebral cortical neuroblasts with survivors showing reduced size, craniofacial dysmorphism, and increased apoptosis in sciatic nerve Schwann cells. The suckling defect was responsible for the death among I-pA1(-/-) neonates and the stunted growth of survivors. Impaired suckling behavior was attributable to defective olfaction, which is likely related to developmental abnormalities in olfactory bulb and/or cerebral cortex. Our results provide evidence that endogenous lysophospholipid signaling requires an Ip receptor gene and indicate that LPA signaling through the LPA1 receptor is required for normal development of an inborn, neonatal behavior.