An essential role for LPA signalling in telencephalon development

TY - JOUR

T1 - An essential role for LPA signalling in telencephalon development

AU - Geach, Timothy J.

AU - Faas, Laura

AU - Devader, Christelle

AU - Gonzalez-Cordero, Anai

AU - Brunsdon, Hannah

AU - tabler, J

AU - Isaacs, Harry V.

AU - Dale, Leslie

N1 - © 2014. Published by The Company of Biologists Ltd. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2014/2

Y1 - 2014/2

N2 - Lysophosphatidic acid (LPA) has wide-ranging effects on many different cell types, acting throughG-protein-coupled receptors such as LPAR6. We show that Xenopus lpar6 is expressed from lateblastulae and is enriched in the mesoderm and dorsal ectoderm of early gastrulae. Expression ingastrulae is an early response to FGF signalling. Transcripts for lpar6 are enriched in the neuralplate of Xenopus neurulae and loss of function caused forebrain defects, with reduced expressionof telencephalic markers (foxg1, emx1 and nkx2-1). Midbrain (en2) and hindbrain (egr2) markerswere unaffected. Foxg1 expression requires LPAR6 within ectoderm and not mesoderm. Headdefects caused by LPAR6 loss of function were enhanced by co-inhibiting FGF signalling, withdefects extending into the hindbrain (en2 and egr2 expression reduced). This is more severe thanexpected from simple summation of individual defects, suggesting that LPAR6 and FGF haveoverlapping or partially redundant functions in the anterior neural plate. We observed similardefects in forebrain development in loss-of-function experiments for ENPP2, an enzyme involvedin the synthesis of extracellular LPA. Our study demonstrates a role for LPA in early forebraindevelopment.

AB - Lysophosphatidic acid (LPA) has wide-ranging effects on many different cell types, acting throughG-protein-coupled receptors such as LPAR6. We show that Xenopus lpar6 is expressed from lateblastulae and is enriched in the mesoderm and dorsal ectoderm of early gastrulae. Expression ingastrulae is an early response to FGF signalling. Transcripts for lpar6 are enriched in the neuralplate of Xenopus neurulae and loss of function caused forebrain defects, with reduced expressionof telencephalic markers (foxg1, emx1 and nkx2-1). Midbrain (en2) and hindbrain (egr2) markerswere unaffected. Foxg1 expression requires LPAR6 within ectoderm and not mesoderm. Headdefects caused by LPAR6 loss of function were enhanced by co-inhibiting FGF signalling, withdefects extending into the hindbrain (en2 and egr2 expression reduced). This is more severe thanexpected from simple summation of individual defects, suggesting that LPAR6 and FGF haveoverlapping or partially redundant functions in the anterior neural plate. We observed similardefects in forebrain development in loss-of-function experiments for ENPP2, an enzyme involvedin the synthesis of extracellular LPA. Our study demonstrates a role for LPA in early forebraindevelopment.

U2 - 10.1242/dev.104901

DO - 10.1242/dev.104901

M3 - Article

SN - 0950-1991

VL - 141

SP - 940

EP - 949

JO - Development

JF - Development

IS - 4

M1 - 104901

ER -