Wnt target gene Ascl4 is dispensable for skin appendage development.

Verdiana Papagno, Ana-Marija Sulic, Jyoti P Satta, Aida Kaffash Hoshiar, Vinod Kumar, Jukka Jernvall, Marja L Mikkola
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Abstract

The development of skin appendages, including hair follicles, teeth and mammary glands is initiated through the formation of the placode, a local thickening of the epithelium. The Wnt/β-catenin signaling cascade is an evolutionary conserved pathway with an essential role in placode morphogenesis, but its downstream targets and their exact functions remain ill defined. In this study, we identify Achaete-scute complex-like 4 (Ascl4) as a novel target of the Wnt/β-catenin pathway and demonstrate its expression pattern in the signaling centers of developing hair follicles and teeth. Ascl transcription factors belong to the superfamily of basic helix-loop-helix transcriptional regulators involved in cell fate determination in many tissues. However, their specific role in the developing skin remains largely unknown. We report that Ascl4 null mice have no overt phenotype. Absence of Ascl4 did not impair hair follicle morphogenesis or hair shaft formation suggesting that it is non-essential for hair follicle development. No tooth or mammary gland abnormalities were detected either. We suggest that other transcription factors may functionally compensate for the absence of Ascl4, but further research is warranted to assess this possibility.

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Wnt靶基因Ascl4对皮肤附属器官的发育是不可或缺的。
皮肤附属物(包括毛囊、牙齿和乳腺)的发育始于胎盘的形成,胎盘是上皮细胞的局部增厚。Wnt/β-catenin信号级联是一条进化保守的通路,在胎盘的形态发生中起着至关重要的作用,但其下游靶点及其确切功能仍未明确。在这项研究中,我们发现Achaete-scute complex-like 4(Ascl4)是Wnt/β-catenin通路的一个新靶点,并证明了它在发育中的毛囊和牙齿信号中心的表达模式。Ascl转录因子属于碱性螺旋-环-螺旋转录调节因子超家族,参与许多组织的细胞命运决定。然而,它们在皮肤发育过程中的具体作用在很大程度上仍然未知。我们报告说,Ascl4无效小鼠没有明显的表型。Ascl4的缺失并不影响毛囊形态发生或毛干的形成,这表明Ascl4对毛囊发育并不重要。也没有发现牙齿或乳腺异常。我们认为,其他转录因子可能会在功能上弥补 Ascl4 的缺失,但还需要进一步的研究来评估这种可能性。
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