title: Retinoid machinery in distinct neural stem cell populations with different retinoid responsiveness.
abstract: Retinoic acid (RA) is present at sites of neurogenesis in both the embryonic and adult brain. While it is widely accepted that RA signaling is involved in the regulation of neural stem cell differentiation, little is known about vitamin A utilization and biosynthesis of active retinoids in the neurogenic niches, or about the details of retinoid metabolism in neural stem cells and differentiating progenies. Here we provide data on retinoid responsiveness and RA production of distinct neural stem cell/neural progenitor populations. In addition, we demonstrate differentiation-related changes in the expression of genes encoding proteins of the retinoid machinery, including components responsible for uptake (Stra6) and storage (Lrat) of vitamin A, transport of retinoids (Rbp4, CrbpI, CrabpI-II), synthesis (Rdh10, Raldh1-4), degradation of RA (Cyp26a1-c1) and RA signaling (Rarα,β,γ, Rxrα,β,γ). We show that both early embryonic neuroectodermal (NE-4C) stem cells and late embryonic or adult derived radial glia like progenitors (RGl cells) are capable to produce bioactive retinoids but respond differently to retinoid signals. However, while neuronal differentiation of RGl cells can not be induced by RA, neuron formation by NE-4C cells is initiated by both RA and RA-precursors (retinol or retinyl acetate). The data indicate that endogenous RA production, at least in some neural stem cell populations, may result in autocrine regulation of neuronal differentiation.
authors.affiliation: 1 Institute of Experimental Medicine , Hungarian Academy of Sciences, Budapest, Hungary .
authors.forename: Barbara
authors.initials: B
authors.lastname: Orsolits
authors.forename: Adrienn
authors.initials: A
authors.lastname: Borsy
authors.forename: Emília
authors.initials: E
authors.lastname: Madarász
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Mészáros
authors.forename: Tímea
authors.initials: T
authors.lastname: Kőhidi
authors.forename: Károly
authors.initials: K
authors.lastname: Markó
authors.forename: Márta
authors.initials: M
authors.lastname: Jelitai
authors.forename: Ervin
authors.initials: E
authors.lastname: Welker
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Környei
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D018168:Receptors, Retinoic Acid; D054840:Retinol-Binding Proteins, Cellular; C108001:Stra6 protein, mouse; D014801:Vitamin A; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase; D000080924:Aldehyde Dehydrogenase 1 Family; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase