Patterning of retinoic acid signaling and cell proliferation in the hippocampus

Abstract

The nuclear receptor ligand retinoic acid (RA) has been identified as an endogenous regulatory factor in the hippocampus, acting on pyramidal neurons and granule neuron progenitors, but almost nothing is known about the distribution of RA itself in the hippocampus. This study describes the source of RA for the rodent hippocampus in the meninges via the key RA synthetic enzyme retinaldehyde dehydrogenase 2 (RALDH2). Diffusion of RA from the meninges potentially creates a gradient of RA across the infrapyramidal and suprapyramidal blades of the dentate gyrus, enhanced by the expression of the RA catabolic enzyme Cyp26B1 between the blades, and an infrapyramidal and suprapyramidal blade difference is evident in RA-regulated transcription. This asymmetry may contribute to some of the physiological and molecular differences between the blades, including a disparity in the rates of cell proliferation in the subgranular zone of the two blades through RA inhibition of cell proliferation. Such differences can be altered by either the application of excess RA, its effect dependent on the relative position along the septotemporal axis, or change in RA signaling through mutation of retinol binding protein, while the capacity of RA to inhibit proliferation of cells in the dentate gyrus is demonstrated using in vitro slice culture. Use of synthetic and catabolic enzymes in the hippocampus to create differing zones of RA concentration parallels the mechanisms used in the developing brain to generate patterns of RA-regulated transcription. © 2012 Wiley Periodicals, Inc.

Thyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes

“…RA has only recently been recognized to be active in the hypothalamus as a regulatory factor and the hypothalamus is one of the few brain regions in which RA functions, alongside regions such as the hippocampus and olfactory system (Goodman et al, 2012; Hagglund et al, 2006; Shearer et al, 2012a). However the importance of RA and its precursor, vitamin A, to control feeding and weight, was recognized much earlier.…”

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

“…Each reaction was run in triplicate on differentiating NE-4C (DIV2, 4,6,10,14), embryonic RGl or adult RGl (DIV4, DIV8) samples, as well as on nondifferentiated NE-4C or RGl (DIV0) samples. Amplification was performed in StepOnePlus (Applied Biosystems) equipment.…”

“…RA has been reported to regulate neuron formation both in the embryonic, as well as in the postnatal/adult brain [1][2][3][4] and has been widely used as a potent inducer of neuronal differentiation in various multipotent cell populations (embryonic carcinoma cells, embryonic and neural stem cells, induced pluripotent stem cells), in vitro.…”

“…Morphogenic roles of retinoids were also demonstrated in the developing forebrain [17][18][19] and the presence and production of RA was described in a subdivision of the developing rostro-ventral telencephalon, the lateral ganglionic eminence [19][20][21]. RAresponsive cells persist in the main neural stem cell niches of the postnatal rodent brain, including the subventricular zone (SVZ) adjacent to the lateral ventricles and the dentate gyrus of the hippocampal formation [2][3][4][22][23][24]. Depletion of RA in adult mice was shown to result in significantly decreased neuronal differentiation within the dentate gyrus [25,26] and RA synthesis seems to regulate proliferation and gene transcription of at least a subset of neural stem cells in the SVZ [27,28].…”

Dynamics of the association of heat shock protein HSPA6 (Hsp70B’) and HSPA1A (Hsp70–1) with stress-sensitive cytoplasmic and nuclear structures in differentiated human neuronal cells

“…Our present study was carried out on SH-SY5Y cells that have been differentiated with retinoic acid to exhibit neuronal features including cessation of cell division, development of long bipolar neuronal-like cellular processes and display of biochemical markers of neuronal differentiation (Pahlman et al 1984;Lopez-Carballo et al 2002; El Andaloussi-Lilja et al 2009). Retinoic acid, which we employ to trigger neuronal differentiation in SH-SY5Y cells, is an endogenous signaling molecule of neuronal differentiation during in vivo development of the nervous system (Jacobs et al 2006;Maden 2007;Goodman et al 2012). Live imaging demonstrated that following thermal stress, both YFP-HSPA6 and YFP-HSPA1A rapidly localized to centrioles in the cytoplasm of differentiated neurons.…”