An essential role for LPA signalling in telencephalon development
| Autor: | Timothy J. Geach, Christelle Devader, Hannah Brunsdon, Harry V. Isaacs, Jacqueline M. Tabler, Anai Gonzalez-Cordero, Laura Faas, Leslie Dale |
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| Rok vydání: | 2014 |
| Předmět: |
Telencephalon
Mesoderm medicine.medical_specialty animal structures Molecular Sequence Data Xenopus Ectoderm Hindbrain Xenopus Proteins FGF and mesoderm formation Xenopus laevis Internal medicine medicine Animals Receptors Lysophosphatidic Acid Molecular Biology DNA Primers Neural Plate biology Base Sequence Reverse Transcriptase Polymerase Chain Reaction Gene Expression Regulation Developmental Gastrula Sequence Analysis DNA biology.organism_classification Microarray Analysis Cell biology Fibroblast Growth Factors medicine.anatomical_structure Endocrinology embryonic structures Forebrain Mesoderm formation Lysophospholipids Neural plate Developmental Biology Signal Transduction |
| Zdroj: | Development (Cambridge, England). 141(4) |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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