An essential role for LPA signalling in telencephalon development.
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.
Department of Cell and Developmental Biology, University College London, Anatomy Building, Gower Street, London, WC1E 6BT, UK.
Timothy J
TJ
Geach
Laura
L
Faas
Christelle
C
Devader
Anai
A
Gonzalez-Cordero
Jacqueline M
JM
Tabler
Hannah
H
Brunsdon
Harry V
HV
Isaacs
Leslie
L
Dale
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005775:Gastrula / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008246:Lysophospholipids / Q000378:metabolism*; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D054258:Neural Plate / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D013687:Telencephalon / Q000196:embryology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*
D017931:DNA Primers; C587665:LPAR6 protein, Xenopus; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D029867:Xenopus Proteins; D005346:Fibroblast Growth Factors; C032881:lysophosphatidic acid
ENPP2; FGF; Forebrain; LPAR6; Telencephalon; Xenopus