scholarly journals Developmental expression of retinoic acid receptors (RARs)

2009 ◽  
Vol 7 (1) ◽  
pp. nrs.07006 ◽  
Author(s):  
Pascal Dollé
Keyword(s):  
Retinoic Acid ◽  
Receptor Gene ◽  
Expression Patterns ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Retinoic Acid Receptors ◽  
Developmental Expression ◽  
Specific Expression ◽  
Functional Studies ◽  
Organ Systems

Here, I review the developmental expression features of genes encoding the retinoic acid receptors (RARs) and the ‘retinoid X’ or rexinoid receptors (RXRs). The first detailed expression studies were performed in the mouse over two decades ago, following the cloning of the murine Rar genes. These studies revealed complex expression features at all stages of post-implantation development, one receptor gene (Rara) showing widespread expression, the two others (Rarb and Rarg) with highly regionalized and/or cell type-specific expression in both neural and non-neural tissues. Rxr genes also have either widespread (Rxra, Rxrb), or highly-restricted (Rxrg) expression patterns. Studies performed in zebrafish and Xenopus demonstrated expression of Rar and Rxr genes (both maternal and zygotic), at early pre-gastrulation stages. The eventual characterization of specific enzymes involved in the synthesis of retinoic acid (retinol/retinaldehyde dehydrogenases), or the triggering of its catabolism (CYP26 cytochrome P450s), all of them showing differential expression patterns, led to a clearer understanding of the phenomenons regulated by retinoic acid signaling during development. Functional studies involving targeted gene disruptions in the mouse, and additional approaches such as dominant negative receptor expression in other models, have pinpointed the specific, versus partly redundant, roles of the RARs and RXRs in many developing organ systems. These pleiotropic roles are summarized hereafter in relationship to the receptors’ expression patterns.

scholarly journals Differential Expression of Melatonin Receptor Subtypes MelIa, MelIb and MelIc in Relation to Melatonin Binding in the Male Songbird Brain

2014 ◽  
Vol 85 (1) ◽  
pp. 4-14 ◽  
Author(s):  
Leonida Fusani ◽  
Manfred Gahr
Keyword(s):  
Expression Patterns ◽  
General Pattern ◽  
Passerine Bird ◽  
Brain Regions ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Melatonin Receptor ◽  
Brain Areas ◽  
Specific Expression

Previous autoradiography studies illustrated that several areas of the avian brain can bind the pineal hormone melatonin. In birds, there are three melatonin receptor (MelR) subtypes: MelIa, MelIb and MelIc. To date, their brain distribution has not been studied in any passerine bird. Therefore, we investigated mRNA distribution of MelR subtypes in adjacent sections of the brain of two songbirds, the blackcap and the zebra finch, in parallel with that of 2-[125I]-iodomelatonin (IMEL) binding sites in the same brains. The general pattern of receptor expression shown by in situ hybridization of species-specific probes matched well with that of IMEL binding. However, the expression of the three subtypes was area specific with similar patterns in the two species. Some brain areas expressed only one receptor subtype, most brain regions co-expressed either MelIa with MelIb or MelIa with MelIc, whereas few areas expressed MelIb and MelIc or all three receptor subtypes. Since many sensory areas, most thalamic areas and subareas of the neopallium, a cortex analogue, express MelR, it is likely that most sensory motor integration functions are melatonin sensitive. Further, the area-specific expression patterns suggest that the regulatory role of melatonin differs among different brain areas. Since subareas of well-defined neural circuits, such as the visual system or the song control system, are equipped with different receptor types, we hypothesize a diversity of functions for melatonin in the control of sensory integration and behavior.

scholarly journals Opioid Receptor Protein Expression During Development of the Rat Brainstem

2021 ◽  
Author(s):  
◽  
Bronwyn Maree Kivell
Keyword(s):  
Confocal Microscopy ◽  
Opioid Receptor ◽  
Glial Cells ◽  
Opioid Receptors ◽  
Cultured Cells ◽  
Expression Patterns ◽  
Receptor Expression ◽  
Developmental Expression ◽  
Receptor Protein ◽  
Western Blots

<p>Few satisfactory protocols exist for primary culture of postnatal brainstem neurons, and commonly used procedures often give poor survival rates in older foetal (>E16) and early postnatal brainstem cultures. The present study describes the first reliable method for establishing stable in vitro cultures of foetal and postnatal brainstem neurons up to six days postnatal age in a defined, serum-free culture medium. This novel culture method was used to study opioid receptor expression and distribution in developing brainstem cells. Opioids play an important role in brainstem functions, being involved in respiratory and cardiovascular modulation and pain control (Olsen et al., 1995; Olson et al., 1997; Vaccarino et al., 1999; Vaccarino and Kastin, 2001). These brainstem functions are particularly important for survival at birth, and opioid receptor distribution patterns and sensitivities to opioid ligands change during development. Using cultured cells and frozen sections of brainstem tissue, mu (MOR) and delta (DOR) opioid receptor localisation in neuronal and glial cells at different stages of foetal and postnatal development in the rat were examined by immunocytochemistry and confocal microscopy. Bipolar and multipolar neurons showed similar immunoreactivities; whereas, glial cells were more lightly stained than neurons. Developmentally advanced stages were more intensely stained for MOR (P<0.006, Mann-Whitney test); whereas, DOR immunoreactivity did not change during development. These developmental expression patterns observed in culture for MOR were similar to those obtained from Western blots of electrophoreses brainstem lysates. DOR, however, decreased in expression in brainstem lysates with increased developmental age, even though there was no difference in DOR expression in cultured cells. MOR and DOR were colocalised in specific brainstem regions and in the cerebellum of foetal and postnatal animals, although the distribution of both opioid receptors in the foetal brain was more diffuse than in the older animals. The intracellular distributions of MOR and DOR were investigated by confocal microscopy. In addition to plasma membrane staining, a population of internalised cytoplasmic receptors was present in neurons. MOR was down-regulated after exposure of either cultured brainstem cells or transfected or non-transfected SH-SY5Y neuroblastoma cells to the MOR agonist DAMGO. From the above investigation, it was concluded that opioid receptors are developmentally regulated during maturation of the brainstem of the rat, and that primary cell culture, immunocytochemistry, and immunoblotting of cell lysates are suitable techniques for investigating opioid systems in the foetal, postnatal, and adult rat.</p>

scholarly journals Characterization of Mice Deficient in the Src Family Nonreceptor Tyrosine Kinase Frk/rak

2002 ◽  
Vol 22 (14) ◽  
pp. 5235-5247 ◽  
Author(s):  
Subhashini Chandrasekharan ◽  
Ting Hu Qiu ◽  
Nawal Alkharouf ◽  
Kelly Brantley ◽  
James B. Mitchell ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Expression Patterns ◽  
Developmental Expression ◽  
Epithelial Tissue ◽  
Intestinal Damage ◽  
Specific Expression ◽  
Nonreceptor Tyrosine Kinase ◽  
Euthyroid Sick Syndrome ◽  
Epithelial Tissues

ABSTRACT Frk/rak belongs to a novel family of Src kinases with epithelial tissue-specific expression. Although developmental expression patterns and functional overexpression in vitro have associated these kinases with growth suppression and differentiation, their physiological functions remain largely unknown. We therefore generated mice carrying a null mutation in iyk, the mouse homolog of Frk/rak. We report here that frk/rak−/− mice are viable, show similar growth rates to wild-type animals, and are fertile. Furthermore, a 2-year study of health and survival did not identify differences in the incidence and spectrum of spontaneous tumors or provide evidence of hyperplasias in frk/rak−/− epithelial tissues. Histological analysis of organs failed to reveal any morphological changes in epithelial tissues that normally express high levels of Frk/rak. Ultrastructural analysis of intestinal enterocytes did not identify defects in brush border morphology or structural polarization, demonstrating that Frk/rak is dispensable for intestinal cytodifferentiation. Additionally, frk/rak-null mice do not display altered sensitivity to intestinal damage induced by ionizing radiation. cDNA microarray analysis revealed an increase in c-src expression and identified subtle changes in the expression of genes regulated by thyroid hormones. Significant decreases in the circulating levels of T3 but not T4 hormone are consistent with this observation and reminiscent of euthyroid sick syndrome, a stress-associated clinical condition.

scholarly journals Opioid Receptor Protein Expression During Development of the Rat Brainstem

2021 ◽  
Author(s):  
◽  
Bronwyn Maree Kivell
Keyword(s):  
Confocal Microscopy ◽  
Opioid Receptor ◽  
Glial Cells ◽  
Opioid Receptors ◽  
Cultured Cells ◽  
Expression Patterns ◽  
Receptor Expression ◽  
Developmental Expression ◽  
Receptor Protein ◽  
Western Blots

<p>Few satisfactory protocols exist for primary culture of postnatal brainstem neurons, and commonly used procedures often give poor survival rates in older foetal (>E16) and early postnatal brainstem cultures. The present study describes the first reliable method for establishing stable in vitro cultures of foetal and postnatal brainstem neurons up to six days postnatal age in a defined, serum-free culture medium. This novel culture method was used to study opioid receptor expression and distribution in developing brainstem cells. Opioids play an important role in brainstem functions, being involved in respiratory and cardiovascular modulation and pain control (Olsen et al., 1995; Olson et al., 1997; Vaccarino et al., 1999; Vaccarino and Kastin, 2001). These brainstem functions are particularly important for survival at birth, and opioid receptor distribution patterns and sensitivities to opioid ligands change during development. Using cultured cells and frozen sections of brainstem tissue, mu (MOR) and delta (DOR) opioid receptor localisation in neuronal and glial cells at different stages of foetal and postnatal development in the rat were examined by immunocytochemistry and confocal microscopy. Bipolar and multipolar neurons showed similar immunoreactivities; whereas, glial cells were more lightly stained than neurons. Developmentally advanced stages were more intensely stained for MOR (P<0.006, Mann-Whitney test); whereas, DOR immunoreactivity did not change during development. These developmental expression patterns observed in culture for MOR were similar to those obtained from Western blots of electrophoreses brainstem lysates. DOR, however, decreased in expression in brainstem lysates with increased developmental age, even though there was no difference in DOR expression in cultured cells. MOR and DOR were colocalised in specific brainstem regions and in the cerebellum of foetal and postnatal animals, although the distribution of both opioid receptors in the foetal brain was more diffuse than in the older animals. The intracellular distributions of MOR and DOR were investigated by confocal microscopy. In addition to plasma membrane staining, a population of internalised cytoplasmic receptors was present in neurons. MOR was down-regulated after exposure of either cultured brainstem cells or transfected or non-transfected SH-SY5Y neuroblastoma cells to the MOR agonist DAMGO. From the above investigation, it was concluded that opioid receptors are developmentally regulated during maturation of the brainstem of the rat, and that primary cell culture, immunocytochemistry, and immunoblotting of cell lysates are suitable techniques for investigating opioid systems in the foetal, postnatal, and adult rat.</p>

Xenopus Hox-2 genes are expressed sequentially after the onset of gastrulation and are differentially inducible by retinoic acid

Development ◽  
1992 ◽  
Vol 116 (Supplement) ◽  
pp. 195-202 ◽  
Author(s):  
Erik-Jan Dekker ◽  
Maria Pannese ◽  
Erwin Houtzager ◽  
Ans Timmermans ◽  
Edoardo Boncinelli ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Expression Patterns ◽  
Positional Information ◽  
Developmental Expression ◽  
Temporal Expression ◽  
Mammalian Cell Lines ◽  
All Trans Retinoic Acid ◽  
Temporal Expression Pattern ◽  
Six Genes ◽  
Chromosomal Sequence

In this paper, we review experiments to characterise the developmental expression and the responses to all-trans retinoic acid (RA) of six members of the Hox-2 complex of homeobox-containing genes, during the early development of Xenopus laevis. We showed that the six genes are expressed in a spatial sequence which is colinear with their putative 3′ to 5′ chromosomal sequence and that five of them are also expressed rapidly after the beginning of gastrulation, in a 3′ to 5′ colinear temporal sequence. The sixth gene (Xhox2.9) has an exceptional spatial and temporal expression pattern. The six genes all respond to RA by showing altered spatiotemporal expression patterns, and are also RA-inducible, the sequence of the magnitudes of their RA responses being colinear with their 3′ to 5′ chromosomal sequence, and with their spatial and temporal expression sequences. Our data also reveal that there is a pre-existing anteroposterior polarity in the embryo's competence for a response to RA. These results complement and extend previous findings made using murine and avian embryos and mammalian cell lines. They suggest that an endogenous retinoid could contribute to positional information in the early Xenopus embryo.

Genomic and proteomic analysis of the myeloid differentiation program

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 513-524 ◽  
Author(s):  
Zheng Lian ◽  
Le Wang ◽  
Shigeru Yamaga ◽  
Wesley Bonds ◽  
Y. Beazer-Barclay ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Bone Marrow Cells ◽  
Retinoic Acid Receptor ◽  
Expression Patterns ◽  
Cell Types ◽  
Dominant Negative ◽  
Myeloid Differentiation ◽  
Mrna Levels ◽  
Murine Bone Marrow

Abstract Although the mature neutrophil is one of the better characterized mammalian cell types, the mechanisms of myeloid differentiation are incompletely understood at the molecular level. A mouse promyelocytic cell line (MPRO), derived from murine bone marrow cells and arrested developmentally by a dominant-negative retinoic acid receptor, morphologically differentiates to mature neutrophils in the presence of 10 μM retinoic acid. An extensive catalog was prepared of the gene expression changes that occur during morphologic maturation. To do this, 3′-end differential display, oligonucleotide chip array hybridization, and 2-dimensional protein electrophoresis were used. A large number of genes whose mRNA levels are modulated during differentiation of MPRO cells were identified. The results suggest the involvement of several transcription regulatory factors not previously implicated in this process, but they also emphasize the importance of events other than the production of new transcription factors. Furthermore, gene expression patterns were compared at the level of mRNA and protein, and the correlation between 2 parameters was studied.

Diversity of expression of engrailed-like antigens in zebrafish

Development ◽  
1991 ◽  
Vol 112 (3) ◽  
pp. 821-832 ◽  
Author(s):  
K. Hatta ◽  
R. Bremiller ◽  
M. Westerfield ◽  
C.B. Kimmel
Keyword(s):  
Expression Patterns ◽  
Cell Types ◽  
Developmental Expression ◽  
Specific Expression ◽  
Pharyngeal Arches ◽  
Neuronal Identity ◽  
Spinal Cord Segment ◽  
Otic Vesicles ◽  
Epidermal Expression ◽  
The Brain

We have studied developmental expression of zebrafish engrailed-like (Eng) antigens. Many cell types are reproducibly labeled by two antibodies that recognize the Eng homeodomain, but other cells are labeled by only one or the other, suggesting a hitherto unrecognized complexity of Eng proteins. Expression patterns vary remarkably according to cell type and location. In the undifferentiated primordia of the brain and of each myotome, expression by a stripe of cells spatially subdivides the primordium at a location where a morphological boundary forms later, suggesting expression may be required for development of the boundaries. Supporting this hypothesis, trunk myotomal cells that express Eng are absent in spt-1 mutant embryos, just where the myotomal boundaries fail to form. Another pattern is present in rhombomeres, pharyngeal arches, and the pectoral girdle. In each of these cases, cells (neuron, muscle, cartilage) generating a subset of a series of repeated elements selectively express Eng. These subsets then form specialized derivatives, suggesting Eng homeoproteins are involved in determining the specializations. Epidermal expression is present in the ventral half of the pectoral fin rudiment, precisely ‘compartmentalizing’ the fin. Neuronal cells at a certain dorsoventral level in each hindbrain and spinal cord segment selectively express Eng, suggesting segmental control of neuronal identity. Specific expression patterns are observed in taste buds, otic vesicles and teeth. Thus we propose that eng genes function in diverse cell types in zebrafish, but play selector roles that can be classified into a few basic types.

NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls β-globin and G-CSF receptor expression

Blood ◽  
2009 ◽  
Vol 114 (9) ◽  
pp. 1753-1763 ◽  
Author(s):  
Linda Marie Starnes ◽  
Antonio Sorrentino ◽  
Elvira Pelosi ◽  
Monica Ballarino ◽  
Ornella Morsilli ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Ectopic Expression ◽  
Receptor Expression ◽  
Specific Expression ◽  
Nuclear Factor I ◽  
Direct Binding ◽  
Normal Human ◽  
Specific Expression Pattern ◽  
Differentiation Pathways ◽  
Transcription Factor Nuclear Factor

Abstract It is generally conceded that selective combinations of transcription factors determine hematopoietic lineage commitment and differentiation. Here we show that in normal human hematopoiesis the transcription factor nuclear factor I-A (NFI-A) exhibits a marked lineage-specific expression pattern: it is upmodulated in the erythroid (E) lineage while fully suppressed in the granulopoietic (G) series. In unilineage E culture of hematopoietic progenitor cells (HPCs), NFI-A overexpression or knockdown accelerates or blocks erythropoiesis, respectively: notably, NFI-A overexpression restores E differentiation in the presence of low or minimal erythropoietin stimulus. Conversely, NFI-A ectopic expression in unilineage G culture induces a sharp inhibition of granulopoiesis. Finally, in bilineage E + G culture, NFI-A overexpression or suppression drives HPCs into the E or G differentiation pathways, respectively. These NFI-A actions are mediated, at least in part, by a dual and opposite transcriptional action: direct binding and activation or repression of the promoters of the β-globin and G-CSF receptor gene, respectively. Altogether, these results indicate that, in early hematopoiesis, the NFI-A expression level acts as a novel factor channeling HPCs into either the E or G lineage.

Retinoic acid receptor expression in human skin keratinocytes and dermal fibroblasts in vitro

1992 ◽  
Vol 102 (1) ◽  
pp. 113-121 ◽  
Author(s):  
C.P. Redfern ◽  
C. Todd
Keyword(s):  
Retinoic Acid ◽  
Expression Patterns ◽  
Phosphodiesterase Inhibitor ◽  
Cell Types ◽  
Dermal Fibroblasts ◽  
Receptor Expression ◽  
Intracellular Camp ◽  
Mrna Levels ◽  
High Calcium

Retinoic acid is essential for the normal differentiation of epithelia but its cellular function is obscure. The expression patterns of retinoic acid receptors (RARs) in skin cell types may give an insight into the role of retinoic acid in skin. We have compared the patterns of RAR expression in human keratinocytes and dermal fibroblasts in vitro, and studied the effects of retinoic acid on RAR expression. RAR-alpha and RAR-gamma were expressed in keratinocytes and fibroblasts: RAR-gamma was expressed at similar levels in both cell types but RAR-alpha was more abundant in fibroblasts. There were no differences in expression of either RAR-alpha or RAR-gamma between stratifying (high-calcium medium) and proliferating (low-calcium medium) keratinocytes and expression of these RARs was unaffected by retinoic acid. RAR-beta was undetectable in keratinocytes. In the majority of fibroblast cell lines, RAR-beta transcripts were either undetectable or expressed at a low level. Retinoic acid at low concentrations (10(−10) to 10(−9) M) rapidly induced the expression of RAR-beta. Cyclic adenosine monophosphate (cAMP) analogues inhibit RAR-beta induction in teratocarcinoma cells. However, dibutyryl-cAMP did not affect RAR-beta induction in fibroblasts. Forskolin, an adenylate cyclase activator, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) decreased constitutive RAR-beta mRNA levels but did not block induction of RAR-beta by retinoic acid. Since intracellular cAMP levels were only increased detectably in response to forskolin, the reduction in constitutive levels of RAR-beta mRNA may be mediated by mechanisms other than via cAMP.

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