Retinoids control anterior and dorsal properties in the developing forebrain
Autor: | Norbert B. Ghyselinck, Aida Halilagic, Vanessa Ribes, Michèle Studer, Maija H. Zile, Pascal Dollé |
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Přispěvatelé: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2007 |
Předmět: |
MESH: Aldehyde Oxidoreductases
MESH: Signal Transduction Indoles MESH: Mice Mutant Strains MESH: Bone Morphogenetic Proteins Retinoic acid Bone Morphogenetic Protein 4 Forebrain morphogenesis Craniofacial Abnormalities Diencephalon chemistry.chemical_compound Mice MESH: Prosencephalon 0302 clinical medicine MESH: Otx Transcription Factors MESH: Gene Expression Regulation Developmental Morphogenesis MESH: Craniofacial Abnormalities MESH: Animals MESH: In Situ Nick-End Labeling In Situ Hybridization MESH: Indoles 0303 health sciences Otx Transcription Factors Vitamin A Deficiency MESH: Retina Gene Expression Regulation Developmental Optic vesicle Aldehyde Oxidoreductases Neural retina Cell biology Bone Morphogenetic Proteins embryonic structures MESH: Microphthalmia-Associated Transcription Factor RPE Signal Transduction medicine.medical_specialty animal structures Fibroblast Growth Factor 8 MESH: T-Box Domain Proteins Biology Quail Retina 03 medical and health sciences Retinoids FGF8 Prosencephalon MESH: In Situ Hybridization Raldh2 Internal medicine Raldh3 MESH: Vitamin A Deficiency medicine In Situ Nick-End Labeling Animals MESH: Retinoids MESH: Galactosides Molecular Biology MESH: Mice 030304 developmental biology VAD quail Microphthalmia-Associated Transcription Factor Eye development MESH: Quail Retinal Dehydrogenase Galactosides MESH: Fibroblast Growth Factor 8 [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology Mice Mutant Strains Signaling MESH: Morphogenesis Endocrinology chemistry Forebrain PAX6 sense organs T-Box Domain Proteins 030217 neurology & neurosurgery Developmental Biology |
Zdroj: | Developmental Biology Developmental Biology, Elsevier, 2007, 303 (1), pp.362-75. ⟨10.1016/j.ydbio.2006.11.021⟩ |
ISSN: | 0012-1606 1095-564X |
Popis: | International audience; We have previously shown that retinoic acid (RA) synthesized by the retinaldehyde dehydrogenase 2 (RALDH2) is required in forebrain development. Deficiency in RA due to inactivation of the mouse Raldh2 gene or to complete absence of retinoids in vitamin-A-deficient (VAD) quails, leads to abnormal morphogenesis of various forebrain derivatives. In this study we show that double Raldh2/Raldh3 mouse mutants have a more severe phenotype in the craniofacial region than single null mutants. In particular, the nasal processes are truncated and the eye abnormalities are exacerbated. It has been previously shown that retinoids act mainly on cell proliferation and survival in the ventral forebrain by regulating SHH and FGF8 signaling. Using the VAD quail model, which survives longer than the Raldh-deficient mouse embryos, we found that retinoids act in maintaining the correct position of anterior and dorsal boundaries in the forebrain by modulating FGF8 anteriorly and WNT signaling dorsally. Furthermore, BMP4 and FGF8 signaling are affected in the nasal region and BMP4 is ventrally expanded in the optic vesicle. At the optic cup stage, Pax6, Tbx5 and Bmp4 are ectopically expressed in the presumptive retinal pigmented epithelium (RPE), while Otx2 and Mitf are not induced, leading to a dorsal transdifferentiation of RPE to neural retina. Therefore, besides being required for survival of ventral structures, retinoids are involved in restricting anterior identity in the telencephalon and dorsal identity in the diencephalon and the retina. |
Databáze: | OpenAIRE |
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