Association between MousenudeGene Expression and the Initiation of Epithelial Terminal Differentiation

Abstract

Loss-of-function mutations in Whn (Hfh 11), a winged-helix/forkhead transcription factor, result in the nude mouse phenotype. To determine the whn expression pattern during development, we utilized mice in which a beta-galactosidase reporter gene was placed under the control of the wild-type whn promoter by homologous recombination (M. Nehls et al., 1996, Science 272, 886-889). Sites of reporter expression were confirmed by immunohistochemical staining for Whn protein or by in situ hybridization for whn mRNA. At all developmental stages, whn expression is restricted to epithelial cells. In addition to the skin and thymus, whn is expressed in the developing nails, nasal passages, tongue, palate, and teeth. In embryonic epidermis, suprabasal cells induce whn expression at the same time that terminal differentiation markers first appear. As the epidermis matures, whn promoter activity is found primarily in the first suprabasal layer, which contains keratinocytes in the early stages of terminal differentiation. In developing and mature anagen hair follicles, whn is expressed at high levels in the postmitotic precursor cells of the hair shaft and inner root sheath. Though principally associated with terminal differentiation, whn expression is also detected in progenitor cell compartments; in the hair bulb matrix and basal epidermal layer, a small subclass of cells expresses whn, while in the outer root sheath, whn promoter activity is induced as the follicle completes its elongation. Within these compartments, rare cells exhibit both whn expression and the nuclear proliferation marker Ki-67. The results suggest that whn expression encompasses the transition from a proliferative to a postmitotic state and that whn regulates the initiation of terminal differentiation.

Epidermal phospholipase Cδ1 regulates granulocyte counts and systemic interleukin-17 levels in mice

“…3d). These expression patterns were consistent with enriched expression of PLCδ1 and Foxn1 in differentiated keratinocytes 29,30 . At the histological level, the introduction of Foxn1::PLCδ1 gene rescued epidermal hyperplasia and immune cell infiltration that were observed in PLCδ1 − / − mice 20 ( Fig.…”

Early Defect Prethymic in Bone Marrow T Cell Progenitors in Athymicnu/nuMice

“…Surprisingly, these Thy1.2 high Lin Ϫ CD2 ϩ cells were markedly reduced in the marrow of nu/nu mice that fail to develop the thymus due to a deficiency in the whn gene, a transcription factor that is critical to the late stage maturation of epithelial cells (22,23). However, this maturation arrest is not caused by the absence of mature T cells in the marrow per se because both CD2…”

“…The whn gene has been shown to be expressed in epithelial cells in mice (22,23) and there is no report of whn expression in lymphoid cells. Therefore, it is unlikely that the defect in the nu/nu Thy1.2 high Lin Ϫ CD2 Ϫ progenitors is due to the expression of the abnormal whn gene in the progenitors themselves.…”

Estudo da expressão temporal e espacial de FoxN1 em modelos biológicos, durante o desenvolvimento embrionário e em jovens adultos

“…(Anexo 1) apresenta um grande número de aminoácidos carregados negativamente e exibe uma alta proporção de resíduos de prolina Lee et al (1999).…”

“…Assim, existindo a mutação em Foxn1, as unhas aparentam estar mais quebradiças e finas em relação ao fenótipo normal. as células epiteliais induzem a expressão de Foxn1 logo que os primeiros sinais de diferenciação terminal começam a aparecer (Lee et al, 1999).…”