Biomedical subjects

Gerard M J Beaudoin

Publications and source records attributed to Gerard M J Beaudoin.

4 recordsLinked to original sources

PubMed2006

Hairless and Wnt signaling: allies in epithelial stem cell differentiation.

Nuclear receptors and Wnt signaling are both important regulators of developmental and physiological processes. Recent work linking these pathways in epithelial stem cell differentiation has come from studies analyzing the in vivo function of the nuclear receptor corepressor, Hairless (HR). The HR protein has long been suspected to regulate a stem cell-mediated process, hair cycling, as mutations in the Hr gene cause hair loss in both mice and men. The discovery that the HR protein is a nuclear receptor corepressor indicated that HR function in hair cycling is by regulating gene expression. A recent study revealed that HR represses expression of Wise, an inhibitor of Wnt signaling, leading to a model in which HR controls the timing of Wnt signaling required for hair cycling. Here we review these data, and provide new data showing that HR corepressor activity is essential for its in vivo function, and identify an additional putative Wnt inhibitor regulated by HR. This work complements previous studies demonstrating the role of Wnt signaling in epithelial stem cell differentiation.

Animals↗

PubMed2006

Con-nectin axons and dendrites.

Unlike adherens junctions, synapses are asymmetric connections, usually between axons and dendrites, that rely on various cell adhesion molecules for structural stability and function. Two cell types of adhesion molecules found at adherens junctions, cadherins and nectins, are thought to mediate homophilic interaction between neighboring cells. In this issue, Togashi et al. (see p. 141) demonstrate that the differential localization of two heterophilic interacting nectins mediates the selective attraction of axons and dendrites in cooperation with cadherins.

Adherens Junctions↗

PubMed2005

Hairless triggers reactivation of hair growth by promoting Wnt signaling.

The mammalian hair cycle involves periodic regeneration of a tiny organ, the hair follicle, through a stem-cell-mediated process. The Hairless (Hr) gene encodes a nuclear receptor corepressor (HR) that is essential for hair follicle regeneration, but its role in this process is unknown. Here, we demonstrate that transgenic expression of HR in progenitor keratinocytes rescues follicle regeneration in Hr(-/-) mice. We show that expression of Wise, a modulator of Wnt signaling, is repressed by HR in these cells, coincident with the timing of follicle regeneration. This work links HR and Wnt function, providing a model in which HR regulates the precise timing of Wnt signaling required for hair follicle regeneration.

Animals↗

PubMed2004

The co-repressor hairless has a role in epithelial cell differentiation in the skin.

Although mutations in the mammalian hairless (Hr) gene result in congenital hair loss disorders in both mice and humans, the precise role of Hr in skin biology remains unknown. We have shown that the protein encoded by Hr (HR) functions as a nuclear receptor co-repressor. To address the role of HR in vivo, we generated a loss-of-function (Hr-/-) mouse model. The Hr-/- phenotype includes both hair loss and severe wrinkling of the skin. Wrinkling is correlated with increased cell proliferation in the epidermis and the presence of dermal cysts. In addition, a normally undifferentiated region, the infundibulum, is transformed into a morphologically distinct structure (utricle) that maintains epidermal function. Analysis of gene expression revealed upregulation of keratinocyte terminal differentiation markers and a novel caspase in Hr-/- skin, substantiating HR action as a co-repressor in vivo. Differences in gene expression occur prior to morphological changes in vivo, as well as in cultured keratinocytes, indicating that aberrant transcriptional regulation contributes to the Hr-/- phenotype. The properties of the cell types present in Hr-/- skin suggest that the normal balance of cell proliferation and differentiation is disrupted, supporting a model in which HR regulates the timing of epithelial cell differentiation in both the epidermis and hair follicle.

Alleles↗