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An essential role for LPA signalling in telencephalon development.

Timothy J Geach1, Laura Faas, Christelle Devader

  • 1Department of Cell and Developmental Biology, University College London, Anatomy Building, Gower Street, London, WC1E 6BT, UK.

Development (Cambridge, England)
|February 6, 2014
PubMed
Summary

Lysophosphatidic acid (LPA) signaling through LPAR6 is crucial for early Xenopus forebrain development. LPA and FGF signaling pathways show overlapping functions in neural plate development.

Keywords:
ENPP2FGFForebrainLPAR6TelencephalonXenopus

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Area of Science:

  • Developmental Biology
  • Neuroscience
  • Cell Signaling

Background:

  • Lysophosphatidic acid (LPA) exerts diverse cellular effects via G-protein-coupled receptors, including LPAR6.
  • LPA signaling is implicated in various biological processes, but its role in early vertebrate brain development remains largely unexplored.

Purpose of the Study:

  • To investigate the role of LPAR6 and LPA signaling in early Xenopus forebrain development.
  • To elucidate the relationship between LPAR6 and Fibroblast Growth Factor (FGF) signaling during neural plate formation.

Main Methods:

  • Expression analysis of Xenopus lpar6 during embryonic development (blastula, gastrula, neurula stages).
  • Loss-of-function experiments using morpholino-mediated knockdown of lpar6 and ENPP2.
  • Analysis of forebrain, midbrain, and hindbrain marker gene expression (foxg1, emx1, nkx2-1, en2, egr2).
  • Combined inhibition of LPAR6 and FGF signaling pathways.

Main Results:

  • Xenopus lpar6 is expressed in mesoderm and dorsal ectoderm during gastrulation, and in the neural plate during neurulation.
  • LPAR6 loss-of-function in Xenopus leads to forebrain defects, characterized by reduced expression of telencephalic markers.
  • LPAR6 acts within the ectoderm to regulate foxg1 expression.
  • Co-inhibition of LPAR6 and FGF signaling exacerbates forebrain defects and impacts hindbrain development, suggesting functional overlap.
  • Loss-of-function of ENPP2, an LPA-synthesizing enzyme, phenocopies LPAR6 loss-of-function defects.

Conclusions:

  • LPA signaling, mediated by LPAR6, plays a significant role in the early development of the Xenopus forebrain.
  • LPAR6 and FGF signaling pathways exhibit overlapping or redundant functions in anterior neural plate patterning.
  • This study highlights a novel role for the LPA signaling pathway in vertebrate neurodevelopment.