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Biomedical subjects

M Houle

Publications and source records attributed to M Houle.

9 recordsLinked to original sources
PubMed2001

RARgamma and Cdx1 interactions in vertebral patterning.

Exogenous retinoic acid (RA) can evoke vertebral homeosis when administered during late gastrulation. These vertebral transformations correlate with alterations of the rostral limit of Hox gene expression in the prevertebrae, suggesting that retinoid signaling regulates the combinatorial expression of Hox genes dictating vertebral identity. Conversely, loss of certain RA receptors (RARs) results in anterior homeotic transformations principally affecting the cervical region. Despite these observations, the relationship between retinoid signaling, somitic Hox expression, and vertebral patterning is poorly understood. The members of the murine Cdx family (Cdx1, Cdx2, and Cdx4) are the homologues of Drosophila caudal and encode homeobox-containing transcription factors. Cdx1 homozygous null mutants exhibit anterior homeotic transformations, some of which are reminiscent of those in RARgamma null offspring. In Cdx1 mutants, these transformations occur concomitant with posteriorized prevertebral expression of certain Hox genes. Cdx1 has recently been demonstrated to be a direct RA target, suggesting an indirect means by which retinoid signaling may impact vertebral patterning. To further investigate this relationship, a complete allelic series of Cdx1-RARgamma mutants was generated and the skeletal phenotype assessed either following normal gestation or after administration of RA. Synergistic interactions between these null alleles were observed in compound mutants, and the full effects of exogenous RA on vertebral morphogenesis required Cdx1. These findings are consistent with a role for RA upstream of Cdx1 as regards axial patterning. However, exogenous RA attenuated several defects inherent to Cdx1 null mutants. This finding, together with the increased phenotypic severity of RARgamma-Cdx1 double null mutants relative to single nulls, suggests that these pathways also function in parallel, likely by converging on common targets.

Animals↗
PubMed2000

Retinoic acid regulation of Cdx1: an indirect mechanism for retinoids and vertebral specification.

Retinoic acid (RA) is required for diverse developmental programs, including vertebral specification. Both RA receptor disruption and excess RA result in homeotic transformations of the axial skeleton. These effects are believed to occur through altered expression of Hox genes, several of which have been demonstrated to be direct RA targets. Members of the cdx (caudal) homeobox gene family are also implicated in regulating Hox expression. Disruption of cdx1 results in vertebral homeotic transformations and alteration of Hox expression boundaries; similar homeosis is also observed in cdx2 heterozygotes. In Xenopus, gain or loss of Cdx function affects vertebral morphogenesis through a mechanism that also correlates with altered Hox expression. Taken together with the finding of putative Cdx binding motifs in several Hox promoters, these data strongly support a role for Cdx members in direct regulation of expression of at least some Hox genes. Most retinoid-responsive Hox genes have not been demonstrated to be direct RA targets, suggesting that intermediaries are involved. Based on these findings, we hypothesized that one or more cdx members may transduce the effects of RA on Hox transcription. Consistent with this, we present evidence that cdx1 is a direct RA target gene, suggesting an additional pathway for retinoid-dependent vertebral specification.

Animals↗
PubMed1999

Hoxd4 and Rarg interact synergistically in the specification of the cervical vertebrae.

We show that, relative to single null mutants, mice bearing mutations in both Hoxd4 and Rarg display malformations of the basioccipital bone, and first (C1) and second cervical vertebrae (C2) at increased penetrance and expressivity, demonstrating synergy between Hoxd4 and Rarg in the specification of the cervical skeleton. In contrast to Rarg mutants, retinoic acid (RA) treatment on embryonic day 10.5 of Hoxd4 single or Hoxd4;Rarg double mutants does not rescue normal development of C2. Somitic expression of Hoxd4 is not altered in wild-type or Rarg mutant animals before or after RA treatment on day 10.5, suggesting that Hoxd4 and Rarg act in parallel to regulate the expression of target genes directing skeletogenesis.

Animals↗
PubMed1999

IL-10 up-regulates CCR5 gene expression in human monocytes.

The chemokine receptor CCR5 has been found to play a key role in early infection with macrophage-tropic isolates of HIV-1 and CCR5 deficiency is associated with a relative resistance to HIV-1 infection. In this context, we studied the regulation of CCR5 gene expression by cytokines, and in particular, interleukin (IL)-10 in human monocytes. CCR5 mRNA was rapidly up-regulated by exposure of monocytes to graded concentrations of IL-10, with near maximal stimulation with 10 ng/ml. The effect was rapid, being detectable as early as 1 h and maximal between 2 and 4 h of treatment. Pretreatment of monocytes with actinomycin D prevented the IL-10-induced effect, suggesting a transcriptional mechanism for CCR5 up-regulation by IL-10. Protein expression of CCR5 was also enhanced by IL-10, as indicated by a 3-fold increase in anti-CCR5 antibody labeling of monocytes treated for 20 h with IL-10. Increased surface expression of CCR5 persisted at 48 h of treatment. Moreover, IL-10-treated monocytes responded with augmented intracellular Ca++ mobilization and enhanced (3-4-fold) chemotaxis in response to the CCR5 ligand MIP-1beta(25 ng/ml). Taken together, our data indicate that IL-10 can modulate CCR5 expression and function. This can constitute a potentially important regulatory mechanism which can affect not only responses during inflammation, but also susceptibility to HIV-1 infection.

Antibodies, Monoclonal↗
PubMed1997

Differential internalization of somatostatin in COS-7 cells transfected with SST1 and SST2 receptor subtypes: a confocal microscopic study using novel fluorescent somatostatin derivatives.

A growing body of evidence suggests that neuropeptide binding to G protein-linked receptors may result in internalization of receptor-ligand complexes, followed by intracellular mobilization and degradation of the ligand into its target cells. Because of discrepant results in the literature concerning the occurrence of such a mechanism for the tetradecapeptide somatostatin (SRIF), we have reinvestigated this question by comparing the binding and internalization of iodinated and fluorescent derivatives of the metabolically stable analog of SRIF, [D-Trp8]SRIF, in COS-7 cells transfected with complementary DNA encoding the sst1 or sst2A receptor subtype. A series of fluoresceinyl and Bodipy fluorescent derivatives of [D-Trp8]SRIF-14 was purified by HPLC, analyzed for purity by mass spectrometry, and tested for biological activity in a membrane binding assay. Of the six compounds tested, fluoresceinyl and Bodipy derivatives labeled in position alpha (fluo-SRIF) retained high affinity for SRIF receptors. COS-7 cells transfected with complementary DNA encoding either sst1 or sst2A receptors both displayed specific, high affinity binding of iodinated and fluo-SRIF. At 4 C, the labeling was confined to the cell surface in both cell types, as indicated by the fact that it was entirely removable by a hypertonic acid wash and assumed a pericellular distribution in the confocal microscope. At 37 C, the fate of specifically bound ligand varied markedly according to the type of receptor transfected. In cells encoding the sst1 receptor, approximately 20% of specifically bound ligand was recovered in the acid-resistant (i.e. intracellular) fraction. This fraction remained clustered at the periphery of the cell, suggesting that it was being sequestered either within or immediately beneath the plasma membrane. By contrast, in cells transfected with sst2A receptors, up to 75% of specifically bound ligand was recovered inside the cells, where it clustered into small endosome-like particles. These particles increased in size and moved toward the nucleus with time, suggestive of receptor-ligand complexes proceeding down the endocytic pathway. These results demonstrate that neuropeptides may be processed differently depending on the subtype of receptor expressed in their target cells and suggest that these different processing patterns may reflect different modes of sensitization/desensitization and recycling of the receptors, and thereby of transmembrane signaling.

Animals↗
PubMed1992

Motives for parenthood and response to failed in vitro fertilization: implications for counseling.

The purpose of this investigation was to identify in vitro fertilization (IVF) candidates' motives for parenthood and hence for seeking treatment. The relationship among identified motives, pretreatment emotional adjustment, and reaction to treatment failure was then examined. Women as a group placed greatest emphasis on fulfilling gender-role requirements, and those strongly endorsing such motives showed the poorest adjustment before IVF and the most negative reaction to first-cycle failure. In contrast, men in general were more likely to stress a desire for marital completion, although this motive was not predictive of emotional status before or after IVF. However, men experiencing social pressures to have children were at greater risk when treatment failed. The results indicate that greater consideration of cognitive factors may enhance understanding of emotional reactions to IVF failure and provide important insights for therapeutic intervention.

Adult↗