The folded cortices were thicker and contained more cells than controls: both more differentiated neurons in the cortical plate and more neural progenitor cells in the ventricular zone. LPA induced terminal mitosis—the generation of neurons from progenitors—and it also reduced apoptotic death of progenitor cells. Although LPA can induce cell proliferation in other systems, Kingsbury et al. saw no increase in S-phase cells, so most of the increase in cell number seemed to be due to inhibition of cell death. The effects of LPA were mediated by one or both of the closely related G protein–coupled receptors LPA1 and LPA2, as cortices from mouse embryos lacking these two receptors did not fold up after LPA treatment.
Neurons in the brain produce LPA, which can activate a number of intracellular signaling pathways. Despite the presence of the LPA signal, however, mice lacking LPA1, LPA2 or both receptors show no evident cortex malformation, suggesting that such signals are not important for the development of the smooth cortex of the mouse. On the other hand, the ability of excess LPA to induce cortical folding in mice suggests the intriguing possibility that LPA might contribute to cortical development in primates.
This is a preview of subscription content, access via your institution
