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PubMed1986

Effects of retinoids in N-nitrosobis(2-oxopropyl)amine-treated hamsters.

The effect of feeding four synthetic retinoids was evaluated in carcinogen-treated hamsters. Syrian golden hamsters were injected with 20 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) and then fed retinoid-supplemented diets for 39 weeks. All retinoid-treated groups grew more slowly than controls, and average survival was shorter in female retinoid-treated groups. A significant incidence of testicular atrophy was noted in male hamsters fed 2-hydroxyethylretinamide or 4-carboxyphenylretinamide. The incidence of pancreatic carcinomas was lower in 12 of 14 retinoid-fed groups than in the corresponding control groups, although the differences approached significance only in groups fed two of the retinoids--male hamsters fed N-4-propionyloxyphenylretinamide and those fed retinylidene dimedone. A low incidence of carcinoma in the control groups limits the conclusions that can be drawn from this study, but it is of note that there was no evidence of promotion.

Adenocarcinoma↗

PubMed1995

LXR, a nuclear receptor that defines a distinct retinoid response pathway.

We have identified a new retinoid response pathway through which 9-cis retinoic acid (9cRA) activates transcription in the presence of LXR alpha, a member of the nuclear receptor superfamily. LXR alpha shows a specific pattern of expression in visceral organs, thereby restricting the response to certain tissues. Retinoid trans-activation occurs selectively on a distinct response element termed an LXRE. Significantly, neither RXR homodimers nor RXR/RAR heterodimers are able to substitute for LXR alpha in mediating this retinoid response. We provide evidence that the retinoid response on the LXRE is the result of a unique interaction between LXR alpha and endogenous RXR, which, unlike in the RXR/RAR heterodimer, makes RXR competent to respond to retinoids. Thus, the interaction with LXR alpha shifts RXR from its role described previously as a silent, DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXREs.

Amino Acid Sequence↗

PubMed1984

Histologic changes in the skin of the rhino mouse (hrrhhrrh) induced by retinoids.

The effects of four retinoids, all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), aromatic retinoid, and arotinoid ethyl ester ( arotinoid ) were examined on the skin of the rhino mouse. Rhino mouse skin is characterized by the presence of keratin-containing utricles attached to the epidermis, and subcutaneous cysts, both of which are derived from hair follicles. The utricles were examined in horizontal sheets of epidermis, and in vertical histologic sections. After applications of 0.1 ml of 0.1% RA, 0.1% 13-cis-RA, 0.1% aromatic retinoid, or 0.001% arotinoid in acetone to the dorsal skin for 5 days a week for 2 weeks, there was a reduction of utricle diameter to 45%, 52%, 30%, and 31% of acetone-treated controls, respectively. Histologic examination of the epidermis revealed that a dose-dependent hyperplasia and thickening of the epidermis and the stratum granulosum was induced by the retinoids when given at subtoxic doses, being most marked after arotinoid or RA. The thickness of the walls of the utricles also increased with increasing dose of retinoid, paralleling the changes in the epidermis. After doses of 0.1% RA and 0.001% arotinoid , the utricles resembled the hair follicles of hairless mice. Hyperplasia of the epidermis appears to be a primary effect of retinoids or rhino mouse skin. Hyperproliferation of the utricle wall is accompanied by a reduction in the size of the utricle lumen, preceding eventual differentiation of the utricles to normal-looking pilar units.

Animals↗

PubMed1995

Transcriptional activation of a model reporter system by retinoids and retinoic acid receptor isoforms.

Retinoic acid (RA) and its congeners mediate their biologic effects after binding to nuclear transcription factors called retinoic acid receptors. Biological effects and binding affinities to various receptors vary widely. Activation of transcription ability for selected retinoids was investigated using a standardized model system. CV-1 cells were cotransfected with a retinoic acid responsive reporter plasmid and expression vectors for retinoic acid receptors (RARs, alpha, beta or gamma) and/or retinoic X receptor (RXR alpha), and were treated with a retinoid (all-trans-RA, 13-cis-RA, Ro 12-4894, SRI 5898-21, or Ro 13-7410). Gene transcription for all retinoids tested was activated in a dose-dependent manner. All-trans-RA was the most potent activator of RAR alpha while SRI 5898-21 was the least active. RAR alpha and RAR beta showed similar levels of activation with all the retinoids tested, Ro 12-4894 and Ro 13-7410 induced little transcription in the presence of RAR gamma. Cotransfection of RXR alpha with the RARs changed the ability of the retinoids to activate transcription. Transcriptional activation in cells cotransfected with RXR and RAR beta or RAR gamma was lower than in cells cotransfected with RAR beta alone or RAR gamma alone. Such models with specific responsive elements may be useful for evaluating the relative activity of various retinoids in vitro, however, complex interactions are likely depending on the choice of the reporter construct and other transcription factors available in the cell.

Base Sequence↗

PubMed1992

The pharmacology of a novel topical retinoid, BMY 30123: comparison with tretinoin.

Preclinical studies pertaining to the pharmacology and toxicology of BMY 30123 (4-acetamidophenyl retinoate) are reported. BMY 30123 is a novel compound which has topical retinoid activity. This compound exhibits lower toxicity, both local and systemic, than other clinically used topical retinoids such as tretinoin (all-trans retinoic acid) in animal models. BMY 30123 is effective in a number of retinoid sensitive skin models including the rhino mouse utriculi reduction assay, the mouse epidermal hyperplasia model and in the suppression of DNA synthesis in mouse skin stimulated with phorbol ester. BMY 30123 was equipotent with tretinoin in these topical models. In the rhino mouse model the ED30 values for BMY 30123 and tretinoin were 0.037 and 0.015 mM, respectively. In addition, BMY 30123 was active in the UVB-induced photodamaged mouse model, another retinoid sensitive model. One of the problems associated with topically applied tretinoin is local irritation. Therefore, for topical therapy to be optimal, it is important to reduce or minimize local irritation. Repeated applications of BMY 30123 to rabbit skin resulted in low skin irritation. The first perceptible signs of skin irritation produced by BMY 30123 occurred at a dose 10 times higher than that observed for tretinoin. BMY 30123 also exhibits low retinoid activity after oral or i.p. administration in mice and produced no signs of hypervitaminosis A-related toxicity at twenty times the no effect dose of tretinoin. Because retinoids are effective modulators of epidermal growth and differentiation, this compound should be useful for the treatment of cutaneous disorders that exhibit altered epidermal differentiation such as acne, psoriasis, ichthyosis and epithelial tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

PubMed2000

Dual mechanisms of action of the retinoid CD437: nuclear retinoic acid receptor-mediated suppression of squamous differentiation and receptor-independent induction of apoptosis in UMSCC22B human head and neck squamous cell carcinoma cells.

The synthetic retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437), which can bind to and activate the nuclear retinoic acid receptors beta and gamma (RARbeta/gamma), is a potent inducer of apoptosis in various cancer cell lines. However, this effect was reported to be independent of RARs. In this study, we compared and contrasted the potencies and mechanisms of action of CD437 and several other receptor-selective retinoids in induction of apoptosis and modulation of squamous differentiation in UMSCC22B human head and neck squamous cell carcinoma cell line. CD437 and the structurally related retinoid CD2325 exhibited almost equal potency in inducing apoptosis, whereas several other retinoids failed to induce apoptosis. The RAR-specific pan antagonist AGN193109 failed to suppress CD437-induced apoptosis, indicating that the induction of apoptosis by CD437 was RAR-independent. c-Fos expression was induced by CD437 and CD2325 that induced apoptosis in the cell line but not by other retinoids that failed to induce apoptosis, suggesting a role for c-Fos in CD437-induced apoptosis. At low concentration (0.01 microM), CD437 shared with several other receptor-selective retinoids the ability to suppress the mRNA levels of the squamous differentiation markers Spr1, involucrin, and cytokeratin 1. This effect of CD437 could be blocked by AGN193109. We conclude that CD437 can exert its effects in UMSCC22B human human head and neck squamous cell carcinoma cells by at least two mechanisms: RAR-mediated suppression of squamous differentiation and RAR-independent induction of apoptosis.

Antineoplastic Agents↗

PubMed1998

Retinoid-induced repression of human immunodeficiency virus type 1 core promoter activity inhibits virus replication.

The rates of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), progression to AIDS following HIV-1 infection, and AIDS-associated mortality are all inversely correlated with serum vitamin A levels (R. D. Semba, W. T. Caiaffa, N. M. H. Graham, S. Cohn, and D. Vlahov, J. Infect. Dis. 171:1196-1202, 1995; R. D. Semba, N. M. H. Graham, W. T. Caiaffa, J. B. Margolik, L. Clement, and D. Vlahov, Arch. Intern. Med. 153:2149-2154, 1993; R. D. Semba, P. G. Miotti, J. D. Chiphangwi, A. J. Saah, J. K. Canner, G. A. Dallabetta, and D. R. Hoover, Lancet 343:1593-1596, 1994). Here we show that physiological concentrations of vitamin A, as retinol or as its metabolite, all-trans retinoic acid, repressed HIV-1Ba-L replication in monocyte-derived macrophages (MDMs). Repression required retinoid treatment of peripheral monocytes during their in vitro differentiation into MDMs. Retinoids had no repressive effect if they were added after virus infection. Retinol, as well as all-trans retinoic acid and 9-cis retinoic acid, also repressed HIV-1 long terminal repeat (LTR)-directed expression up to 200-fold in transfected THP-1 monocytes. Analysis of HIV-1 LTR deletion mutants demonstrated that retinoids were able to repress activation of HIV-1 expression by both NF-kappaB and Tat. A cis-acting sequence required for retinoid-mediated repression of HIV-1 transcription was localized between nucleotides -51 and +12 of the HIV-1 LTR within the core promoter. Protein-DNA cross-linking experiments identified four proteins specific to retinoid-treated cells that bound to the core promoter. We conclude that retinoids render macrophages resistant to virus replication by modulating the interaction of cellular transcription factors with the viral core promoter.

Cell Differentiation↗

PubMed2004

Transplacental delivery of retinoid: the role of retinol-binding protein and lipoprotein retinyl ester.

Retinoids are required for normal embryonic development. Both embryonic retinoid deficiency and excess result in congenital malformations. There is little understanding of the physiology underlying retinoid transfer from the maternal circulation to the embryo. We now report studies that explore this process using retinol-binding protein-deficient (RBP-/-) mice and mice that express human RBP on the RBP-/-) background. Our studies establish that dietary retinoid, bound to lipoproteins, can serve as an important source for meeting tissue retinoid requirements during embryogenesis. Indeed, retinyl ester concentrations in the circulations of pregnant RBP-/- mice are significantly elevated over those observed in wild-type mice, suggesting that lipoprotein retinyl esters may compensate for the absence of retinol-RBP during pregnancy. We also demonstrate, contrary to earlier proposals, that maternal RBP does not cross the placenta and cannot enter the fetal circulation. Overall, our data indicate that both retinol-RBP and retinyl esters bound to lipoproteins are able to provide sufficient retinoid to the embryo to allow for normal embryonic development.

Analysis of Variance↗

PubMed2004

The retinoid antagonist MX781 induces clusterin expression in prostate cancer cells via heat shock factor-1 and activator protein-1 transcription factors.

Retinoids mediate numerous biological responses through the transcriptional activation of nuclear retinoid receptors. Due to their antiproliferative activity, retinoids have shown promise as anticancer agents. Synthetic analogs have been described that selectively activate one subset of the retinoid receptors or inhibit their transcriptional activity. Some of these compounds exhibit strong anticancer activity, which is associated with their ability to induce apoptosis. Here we describe that the retinoid antagonist MX781 causes a substantial increase of clusterin mRNA and protein levels in prostate carcinoma cells. In contrast, retinoic acid and other synthetic agonists and antagonists show no effect on clusterin mRNA/protein levels. Induction of clusterin mRNA is associated with transcriptional activation of the clusterin promoter, which requires the proximal -218-bp region containing binding sites for heat shock factor (HSF)-1, activator protein (AP)-2, and AP-1 transcription factors. MX781 slightly induces AP-1 DNA binding activity, and mutation of the AP-1 site differentially affects the activation of the clusterin promoter in a cell type-specific manner. In contrast, a robust increase of HSF-1 DNA binding activity is observed in all cancer cell lines examined, and mutation of the heat shock element site in the clusterin promoter completely abolishes MX781-induced transcriptional activation in PC3 and DU145 cells. Other agonist retinoid-related molecules also induce AP-1 activity, but not HSF-1, and elicit no effect on clusterin expression levels. These data point to HSF-1 as an important factor regulating clusterin expression in response to MX781, although AP-1 activity may also participate in a cell type-specific manner.

Apoptosis↗

PubMed1999

What are natural retinoids?

Vitamin A (retinol) is the prototype of all other natural retinoids. It is composed of a nonaromatic ring structure, a polyprenoid side chain and a carbonyl end group. These features make it liable to metabolic interconversion and protein interactions but also cause detergent-like properties and a sensitivity to UV irradiation and oxidation. Natural retinoids are present in all living organisms, either as preformed vitamin A or as carotenoids, and are required for a vast number of biological processes, e.g. vision, cellular growth and differentiation and reproduction. Although retinol is the most omnipotent compound, natural retinoids like all-trans-, 9-cis- and didehydroretinoic acid (RA) are clearly more potent outside the retina and trigger gene expression via binding to nuclear retinoid receptors. Retinaldehyde takes an intermediate position in this respect, with ability to convert to both retinol and RA. Over the years, many natural retinoids have been tried therapeutically against skin disorders with the best effects achieved with retinol, retinaldehyde, 13-cis-RA and all-trans-RA. The latter compound was the prototype when new, synthetic derivatives of vitamin A were sought, hoping for a better therapeutic index and a higher functional specificity. Inevitably, treatment with such drugs will influence the effects of coexisting natural retinoids. An understanding of the basic principles of these interactions may have major impact on patient outcome.

Carotenoids↗

PubMed2005

Retinoid concentrations in the mouse during postnatal development and after maternal vitamin A supplementation.

BACKGROUND: Vitamin A (VA) and its derivates (retinoids) are important nutritional substances, which mediate their biological activity mainly via nuclear retinoid receptors. Maternal VA intake during lactation influences the VA content in milk and the VA status of the progeny. We investigated the effects of maternal supplementation during lactation and direct supplementation to the pups after weaning on the retinoid concentration in serum and liver of neonatal mice using high doses of VA. METHODS: Dams were fed a basal (4,500 retinol equivalents/kg diet) or a VA-supplemented (324,000 retinol equivalents/kg diet) diet during lactation. Pups kept receiving the same diet after weaning. Serum and liver samples of the pups were collected during lactation at days 1, 3, 5, 7, and 14 and post-weaning at days 21 and 65 after birth. Samples were analysed for retinoids by high-performance liquid chromatography. RESULTS: Maternal VA supplementation resulted in significantly higher concentrations of retinol, retinyl palmitate and retinyl stearate in serum of mice neonates at days 5, 7, 14, 21 and 65 after birth in comparison to the basal diet, whereas significantly higher concentrations were observed in liver at days 5, 14, 21 and 65 after birth. At day 7 after birth, a decrease in the liver retinoid concentrations occurred in the VA-supplemented diet. CONCLUSION: Our results show for the first time that supplementation with high doses of VA during the lactation period in mice can affect serum retinol concentrations in the neonates and report that day 7 after birth is a critical time in the tissue distribution of retinoids during postnatal development.

Animal Feed↗

PubMed1995

Retinoids and sebaceous gland activity.

BACKGROUND AND OBJECTIVE: The marked efficacy of isotretinoin in the treatment of acne is undoubtedly due to its potential to inhibit sebaceous gland activity. The question arises if the anti-acne effect of new oral retinoids can be predicted by using the currently available experimental models. METHODS: We reviewed the effects of various oral retinoids on sebum excretion in humans and their efficacy in acne. The human data were compared to the results obtained from in vitro and animal models. RESULTS: Oral retinoids such as etretinate, acitretin and the so-called arotinoids were not able to inhibit the sebum production in humans and were ineffective against acne. In various animal models (i.e. sebum production in rats, flank organ size in hamsters, ear sebaceous gland size in hamster, most of these retinoids were shown to be effective. Furthermore, in addition to isotretinoin, some retinoids were able to suppress the proliferation of human sebocytes in vitro. CONCLUSIONS: The elucidation of the mechanism of action of isotretinoin on the sebocyte biology is critical for the search of more reliable models and for the discovery of new retinoids with anti-acne activity.

Acne Vulgaris↗

PubMed1987

Retinoid effects on the epidermis.

Since metaplasia and gap junction stimulation are prominent features of retinoid activity in embryonic and neoplastic epidermis, it is ironic that the mechanism(s) of retinoid action in postnatal tissues, where these drugs are employed clinically, appears to be different. Histologic studies in both animals and man with both topical and systemic retinoids demonstrate acanthosis, hypergranulosis, and changes in the thickness and organization of the stratum corneum, due to a boost in cell turnover. On an ultrastructural level, desmosomes are actively shed at the level of the spinous layer, leading to many new attachment points along the cell membranes of the outer epidermis. This change coupled with decreased tonofilaments, enhanced keratinocyte autolysis, and intercellular deposition of glycoconjugates (not mucin by standard histochemistry and lectin binding) lead to loosening and fragility of the stratum corneum. The biochemical basis of retinoid activity (in addition to increased cell turnover) appears to be global enhancement of glycoconjugate synthesis and the generation of less mature keratins. These epidermal effects of retinoids can be exploited therapeutically: (1) to cause loosening of thickened stratum corneum, e.g., in psoriasis or ichthyosis; (2) to enhance penetration of pharmacologic agents, e.g., 5-FU, across hypertrophic actinic keratoses; and finally (3) in neoplastic epidermis, where mucous metaplasia and gap junction proliferation occur, retinoids can normalize differentiation.

Animals↗

PubMed2001

Retinoids inhibit proliferation of human coronary smooth muscle cells by modulating cell cycle regulators.

Retinoids inhibit rat vascular smooth muscle cell (VSMC) proliferation in vitro and intimal hyperplasia in vivo. We examined the mechanism of the antiproliferative effect of retinoids on human coronary artery smooth muscle cells (human CASMCs). The RAR ligands all-trans-retinoic acid (atRA) and ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-l-propenyl]-benzoic acid (TTNPB); a pan-RXR/RAR agonist, 9-cis-retinoic acid (9cRA); and the RXR-selective ligand AGN4204 all inhibited DNA synthesis stimulated with platelet-derived growth factor and insulin (IC(50): TTNPB 63 nmol/L, atRA 120 nmol/L, AGN4204 460 nmol/L, 9cRA 1.5 micromol/L). All retinoids blocked cell cycle progression as determined by flow cytometry and inhibited retinoblastoma protein (Rb) phosphorylation. TTNPB, atRA, and AGN4204 inhibited the mitogenic induction of cyclin D1, whereas 9cRA had no effect. None of the retinoids affected the expression of CDK 2, 4, or 6 or cyclin E. All retinoids attenuated mitogen-induced downregulation of CDKI p27(Kip1), a major negative regulator of Rb phosphorylation, partly through stabilizing p27(Kip1) turnover. These data demonstrate that retinoids have antiproliferative activity by modulating G(1) --> S cell cycle regulators in human CASMCs through inhibition of Rb phosphorylation and elevation of p27(Kip1) levels.

Cell Cycle Proteins↗

PubMed1987

Regulation of the expression of tissue inhibitor of metalloproteinases and collagenase by retinoids and glucocorticoids in human fibroblasts.

The regulation of the expression of interstitial collagenase and tissue inhibitor of metalloproteinases (TIMP) was examined in response to both retinoid compounds and glucocorticoids. Effective retinoids induced a dose-dependent, specific increase in the production of TIMP of approximately two- to threefold by monolayer cultures of human fibroblasts derived from various tissues, while simultaneously causing a decrease in collagenase secretion of similar magnitude. These effects were apparent by 8-12 h in culture and disappeared within 24 h after the withdrawal of retinoid compounds. The retinoid effect on TIMP production was mediated via an increased biosynthesis of new inhibitor protein. Similarly, increased steady state levels of TIMP messenger RNA (mRNA) accompanied by decreased quantities of collagenase mRNA were demonstrated, suggesting transcriptional control of the retinoid action. The data suggest that retinoids co-regulate the expression of collagenase and TIMP, and do so in an inverse manner. Dexamethasone caused a dose-dependent, specific decrease in collagenase production without altering the biosynthesis of TIMP. These findings were paralleled by a marked reduction in collagenase mRNA, without any accompanying change in TIMP mRNA. Therefore, TIMP and collagenase expression appear to be independently modulated by glucocorticoids.

Cell Line↗

PubMed1992

The role of retinoids in normal and abnormal embryonic craniofacial morphogenesis.

The objective of this article is to evaluate the role of retinoids in the developing head and face. This article covers two lines of evidence that strongly support a role for retinoids in craniofacial development. First, the specific effects of exogenous retinoids on the head and face are covered and mechanisms for the specificity discussed. Second, the function of endogenous retinoids in facial development is discussed in relation to the distribution of retinoid-binding substances in the face. Finally, the interaction of retinoids with other genes known to be expressed in the face as well as other factors required for facial growth is discussed.

Animals↗

PubMed1999

Action of retinoids on embryonic and early postnatal testis development.

The current study investigates the hypothesis that retinoids have a role in embryonic testis development. The action of retinoids on testis development and the expression of retinoic acid receptors (RAR alpha, RAR beta, RAR gamma) were examined. In embryonic day 13 (E13; plug date = E0) testis organ cultures an RAR-selective agonist and all-trans retinoic acid completely inhibited seminiferous cord formation. In contrast, an RAR alpha-selective antagonist had no effect. RT-PCR demonstrated that RAR alpha messenger RNA (mRNA) was expressed at all developmental time points evaluated, which included embryonic day 14 (E14) through postnatal day 30 (P30). Expression of RAR beta mRNA was present at E15 through P2, whereas RAR gamma mRNA was expressed at E18 through P2. Cellular localization of receptors by immunohistochemistry indicated that RAR alpha was localized to the interstitium at E18 and to the seminiferous cords by P0. RAR beta and RAR gamma were detected in both interstitium and cords at E16 and by E18 were mainly expressed in the cords. At P0 RAR beta and RAR gamma were localized to the germ cell populations. To examine retinoid actions, the growth of P0 testis cultures were investigated. Interestingly, retinol and retinoic acid did not inhibit growth of P0 testis cultures but did inhibit the action of growth stimulators. Retinoic acid inhibited FSH, EGF, and 10% calf serum stimulated growth in P0 testis cultures. The hypothesis tested was that the inhibitory effects of retinoids on P0 testis growth may be mediated through the growth inhibitor, transforming growth factor-beta (TGF beta). The action of retinoids on TGF beta mRNA expression was examined in P0 testis cultures. Retinoic acid stimulated TGFbeta3 mRNA expression within 24 h and increased expression of TGFbeta1 and TGFbeta2 after 72 h. Retinol increased expression of TGFbeta1 and TGFbeta2 but not TGFbeta3 after 72 h of treatment. These observations indicate that retinoic acid can influence seminiferous cord formation and testis growth. The inhibitory actions of retinoids may in part be mediated through increased expression of TGFbeta isoforms.

Animals↗

PubMed1999

Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation.

In order to identify molecular mechanisms involved in striatal development, we employed a subtraction cloning strategy to enrich for genes expressed in the lateral versus the medial ganglionic eminence. Using this approach, the homeobox gene Meis2 was found highly expressed in the lateral ganglionic eminence and developing striatum. Since Meis2 has recently been shown to be upregulated by retinoic acid in P19 EC cells (Oulad-Abdelghani, M., Chazaud, C., Bouillet, P., Sapin, V., Chambon, P. and Dollé, P. (1997) Dev. Dyn. 210, 173-183), we examined a potential role for retinoids in striatal development. Our results demonstrate that the lateral ganglionic eminence, unlike its medial counterpart or the adjacent cerebral cortex, is a localized source of retinoids. Interestingly, glia (likely radial glia) in the lateral ganglionic eminence appear to be a major source of retinoids. Thus, as lateral ganglionic eminence cells migrate along radial glial fibers into the developing striatum, retinoids from these glial cells could exert an effect on striatal neuron differentiation. Indeed, the treatment of lateral ganglionic eminence cells with retinoic acid or agonists for the retinoic acid receptors or retinoid X receptors, specifically enhances their striatal neuron characteristics. These findings, therefore, strongly support the notion that local retinoid signalling within the lateral ganglionic eminence regulates striatal neuron differentiation.

Animals↗