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Development February 1, 2014; 141 (4): 940-9.

An essential role for LPA signalling in telencephalon development.

Geach TJ , Faas L , Devader C , Gonzalez-Cordero A , Tabler JM , Brunsdon H , Isaacs HV , Dale L .

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

PubMed ID: 24496630
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cdx4 egr2 emx1 emx1l en2 enpp2 fgf4 fgf8 fgfr1 foxg1 gnl3 krt12.4 lpar6 mapk1 myc myod1 nkx2-1 odc1 otx2 pax6 rax snai2 sox2 tbxt
Antibodies: Mapk1 Ab3
Morpholinos: enpp2 MO1

Article Images: [+] show captions