Journal article
Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior
Proceedings of the National Academy of Sciences - PNAS, Vol.97(24), pp.13384-13389
11/21/2000
DOI: 10.1073/pnas.97.24.13384
PMCID: PMC27233
PMID: 11087877
Abstract
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, lpA1/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 lpA1 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 lpA1(2/2) 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 lp receptor gene and indicate that LPA signaling through the LPA1 receptor is required for normal development of an inborn, neonatal behavior.
Details
- Title: Subtitle
- Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior
- Creators
- James J. A Contos - Biomedical Sciences Program, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0636Nobuyuki Fukushima - Biomedical Sciences Program, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0636Joshua A Weiner - Biomedical Sciences Program, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0636Dhruv Kaushal - Biomedical Sciences Program, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0636Jerold Chun - Biomedical Sciences Program, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0636
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.97(24), pp.13384-13389
- DOI
- 10.1073/pnas.97.24.13384
- PMID
- 11087877
- PMCID
- PMC27233
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 11/21/2000
- Academic Unit
- Liberal Arts and Science Admin; Psychiatry; Iowa Neuroscience Institute; Biology
- Record Identifier
- 9983997983302771
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