An essential role for LPA signalling in telencephalon development

Timothy J. Geach, Laura Faas, Christelle Devader, Anai Gonzalez-Cordero, Hannah Brunsdon, J tabler, Harry V. Isaacs, Leslie Dale

Research output: Contribution to journalArticlepeer-review


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
Original languageEnglish
Article number104901
Pages (from-to)940-949
Number of pages10
Issue number4
Publication statusPublished - Feb 2014

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