The oxidizing enzyme CYP26a1 tightly regulates the availability of retinoic acid in the gastrulating mouse embryo to ensure proper head development and vasculogenesis

Autor: Martin Petkovich, Valérie Fraulob, Vanessa Ribes, Pascal Dollé
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: Oxidation-Reduction
MESH: Mice
Mutant Strains
MESH: Allantois
Retinoic acid
chemistry.chemical_compound
Mice
MESH: Prosencephalon
0302 clinical medicine
Cytochrome P-450 Enzyme System
Allantois
MESH: Embryonic Development
MESH: Animals
0303 health sciences
Cell Differentiation
MESH: Rhombencephalon
Retinoic Acid 4-Hydroxylase
Cell biology
medicine.anatomical_structure
embryonic structures
MESH: Cytochrome P-450 Enzyme System
Endoderm
Neural plate
Oxidation-Reduction
MESH: Body Patterning
MESH: Cell Differentiation
medicine.medical_specialty
Mesoderm
Embryonic Development
Hindbrain
Tretinoin
Biology
03 medical and health sciences
Prosencephalon
Internal medicine
MESH: Gastrula
medicine
Animals
MESH: Mice
030304 developmental biology
Body Patterning
MESH: Tretinoin
Embryogenesis
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
Gastrula
Mice
Mutant Strains
Gastrulation
Rhombencephalon
Endocrinology
chemistry
Epiblast
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Developmental Dynamics
Developmental Dynamics, Wiley, 2007, 236 (3), pp.644-53. ⟨10.1002/dvdy.21057⟩
ISSN: 1058-8388
1097-0177
DOI: 10.1002/dvdy.21057⟩
Popis: Retinoic acid (RA) has been implicated as one of the signals providing a posterior character to the developing vertebrate central nervous system. Embryonic RA first appears in the posterior region of the gastrulating embryo up to the node level, where it may signal within the adjacent epiblast and/or newly induced neural plate to induce a hindbrain and spinal cord fate. Conversely, rostral head development requires forebrain-inducing signals produced by the anterior visceral endoderm and/or prechordal mesoderm, and there is evidence that RA receptors must be in an unliganded state to ensure proper head development. As RA is a diffusible lipophilic molecule, some mechanism(s) must therefore have evolved to prevent activation of RA targets in anterior regions of the embryo. This might result from RA catabolism mediated by the CYP26A1 oxidizing enzyme, which is transiently expressed in anteriormost embryonic tissues; however, previous analysis of Cyp26a1(-/-) mouse mutants did not clearly support this hypothesis. Here we show that Cyp26a1(-/-) null mutants undergo head truncations when exposed to maternally-derived RA, at doses that do not affect wild-type head development. These anomalies are linked to a widespread ectopic RA signaling activity in rostral head tissues of CYP26A1-deficient embryos. Thus, CYP26A1 is required in the anterior region of the gastrulating mouse embryo to prevent teratological effects that may result from RA signaling. We also report a novel role of CYP26A1 during early development of the intra- and extra-embryonic vascular networks.
Databáze: OpenAIRE
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