ArticleMechanisms of development2005
Requirement of mesodermal retinoic acid generated by Raldh2 for posterior neural transformation.
Article in Mechanisms of development, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 108 citations in OpenAlex.
- Folate deficiency disrupts key metabolic transitions within the developing neural ectoderm.bioRxiv : the preprint server for biology · 2026Article
- Retinoic acid and FGF signaling interact to control elongation and lineage specification in a mouse gastruloid model.Development (Cambridge, England) · 2026Article
- Modelling co-development between the somites and neural tube in human trunk-like structures.Nature cell biology · 2025Article
- Early retinoic acid signaling organizes the body axis and defines domains for the forelimb and eye.Current topics in developmental biology · 2025Review
- Rewiring of the epigenome and chromatin architecture by exogenously induced retinoic acid signaling during zebrafish embryonic development.Nucleic acids research · 2024Article
- Sall4 regulates posterior trunk mesoderm development by promoting mesodermal gene expression and repressing neural genes in the mesoderm.Development (Cambridge, England) · 2024Article
- Caudal Fgfr1 disruption produces localised spinal mis-patterning and a terminal myelocystocele-like phenotype in mice.Development (Cambridge, England) · 2023Article
- Retinoic acid, RARs and early development.Journal of molecular endocrinology · 2022Article
- Anterior patterning genes induced by Zic1 are sensitive to retinoic acid and its metabolite, 4-oxo-RA.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Forebrain Organoids to Model the Cell Biology of Basal Radial Glia in Neurodevelopmental Disorders and Brain Evolution.Frontiers in cell and developmental biology · 2022Review
- Stem Cell Neurodevelopmental Solutions for Restorative Treatments of the Human Trunk and Spine.Frontiers in cellular neuroscience · 2021Article
- Retinoid signaling in skeletal development: Scoping the system for predictive toxicology.Reproductive toxicology (Elmsford, N.Y.) · 2021Review
- Mesoderm patterning by a dynamic gradient of retinoic acid signalling.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Review
- Retinoids and developmental neurotoxicity: Utilizing toxicogenomics to enhance adverse outcome pathways and testing strategies.Reproductive toxicology (Elmsford, N.Y.) · 2020Review
- Molecular characterization of a toxicological tipping point during human stem cell differentiation.Reproductive toxicology (Elmsford, N.Y.) · 2020Article
- Retinoic acid signaling pathways.Development (Cambridge, England) · 2019Review
- Sonic Hedgehog Signaling Is Required for Cyp26 Expression during Embryonic Development.International journal of molecular sciences · 2019Article
- Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells.Stem cell reports · 2018Article
- Generating retinoic acid gradients by local degradation during craniofacial development: One cell's cue is another cell's poison.Genesis (New York, N.Y. : 2000) · 2018Review
- Distinct retinoic acid receptor (RAR) isotypes control differentiation of embryonal carcinoma cells to dopaminergic or striatopallidal medium spiny neurons.Scientific reports · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Studies in amphibian embryos have suggested that retinoic acid (RA) may function as a signal that stimulates posterior differentiation of the nervous system as postulated by the activation-transformation model for anteroposterior patterning of the nervous system. We have tested this hypothesis in retinaldehyde dehydrogenase-2 (Raldh2) null mutant mice lacking RA synthesis in the somitic mesoderm. Raldh2(-/-) embryos exhibited neural induction (activation) as evidenced by expression of Sox1 and Sox2 along the neural plate, but differentiation of spinal cord neuroectodermal progenitor cells (posterior transformation) did not occur as demonstrated by a loss of Pax6 and Olig2 expression along the posterior neural plate. Spinal cord differentiation in Raldh2(-/-) embryos was rescued by maternal RA administration, and during the rescue RA was found to act directly in the neuroectoderm but not the somitic mesoderm. RA generated by Raldh2 in the somitic mesoderm was found to normally travel as a signal throughout the mesoderm and neuroectoderm of the trunk and into tailbud neuroectoderm, but not into tailbud mesoderm. Raldh2(-/-) embryos also exhibited increased Fgf8 expression in the tailbud, and decreased cell proliferation in tailbud neuroectoderm. Our findings demonstrate that RA synthesized in the somitic mesoderm is necessary for posterior neural transformation in the mouse and that Raldh2 provides the only source of RA for posterior development. An important concept to emerge from our studies is that the somitic mesodermal RA signal acts in the neuroectoderm but not mesoderm to generate a spinal cord fate.
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