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.
Kingsbury
Marcy A
MA
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, ICND 118, La Jolla, California 92037, USA.
Rehen
Stevens K
SK
Contos
James J A
JJ
Higgins
Christine M
CM
Chun
Jerold
J
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development*; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D049368:Receptors, Lysophosphatidic Acid
D006131:Growth Inhibitors; D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid