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Estivill-Torrús, Guillermo; Llebrez-Zayas, Pedro; Matas-Rico, Elisa; Santín, Luis; Pedraza, Carmen; De Diego, Isabel; Del Arco, Ignacio; Fernández-Llebrez, Pedro; Chun, Jerold; De Fonseca, Fernando Rodríguez
Cerebral cortex (New York, N.Y. 1991) 18, Številka: 4Journal Article
Lysophosphatidic acid (LPA) is a simple phospholipid with extracellular signaling properties mediated by specific G protein–coupled receptors. At least 2 LPA receptors, LPA1 and LPA2, are expressed in the developing brain, the former enriched in the neurogenic ventricular zone (VZ), suggesting a normal role in neurogenesis. Despite numerous studies reporting the effects of exogenous LPA using in vitro neural models, the first LPA1 loss-of-function mutants reported did not show gross cerebral cortical defects in the 50% that survived perinatal demise. Here, we report a role for LPA1 in cortical neural precursors resulting from analysis of a variant of a previously characterized LPA1-null mutant that arose spontaneously during colony expansion. These LPA1-null mice, termed maLPA1, exhibit almost complete perinatal viability and show a reduced VZ, altered neuronal markers, and increased cortical cell death that results in a loss of cortical layer cellularity in adults. These data support LPA1 function in normal cortical development and suggest that the presence of genetic modifiers of LPA1 influences cerebral cortical development.
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