Retinoid Machinery in Distinct Neural Stem Cell Populations with Different Retinoid Responsiveness

Orsolits, Barbara and Borsy, Adrienn Éva and Madarász, Emilia and Mészáros, Zsófia and Kőhidi, Tímea and Markó, Károly and Jelitai, Márta and Welker, Ervin and Környei, Zsuzsanna (2013) Retinoid Machinery in Distinct Neural Stem Cell Populations with Different Retinoid Responsiveness. STEM CELLS AND DEVELOPMENT, 22 (20). pp. 2777-2793. ISSN 1547-3287

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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 (Raralpha,beta,gamma, Rxralpha,beta,gamma). 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.

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