Non-proliferative effects of lysophosphatidic acid enhance cortical growth and folding

Lysophosphatidic acid (LPA) is a phospholipid that has extracellular signaling properties mediated by G protein-coupled receptors. Two LPA receptors, LPA(1) and LPA(2), are expressed in the embryonic cerebral cortex, suggesting roles for LPA signaling in cortical formation. Here we report that intact cerebral cortices exposed to extracellular LPA ex vivo rapidly increased in width and produced folds resembling gyri, which are not normally present in mouse brains and are absent in LPA(1) LPA(2) double-null mice. Mechanistically, growth was not due to increased proliferation but rather to receptor-dependent reduced cell death and increased terminal mitosis of neural progenitor cells (NPCs). Our results implicate extracellular lipid signals as new influences on brain formation during embryonic development.