Morosan-Puopolo Gabriela, Balakrishnan-Renuka Ajeesh, Yusuf Faisal, Chen Jingchen, Dai Fangping, Zoidl Georg, Lüdtke Timo H-W, Kispert Andreas, Theiss Carsten, Abdelsabour-Khalaf Mohammed, Brand-Saberi Beate
Department of Anatomy and Molecular Embryology, Ruhr-University of Bochum, Bochum, Germany; Department of Molecular Embryology, Freiburg University, Freiburg, Germany; Faculty of Biology, Freiburg University, Freiburg, Germany.
Department of Anatomy and Molecular Embryology, Ruhr-University of Bochum, Bochum, Germany.
PLoS One. 2014 Mar 26;9(3):e92679. doi: 10.1371/journal.pone.0092679. eCollection 2014.
The embryonic origin of the dermis in vertebrates can be traced back to the dermomyotome of the somites, the lateral plate mesoderm and the neural crest. The dermal precursors directly overlying the neural tube display a unique dense arrangement and are the first to induce skin appendage formation in vertebrate embryos. These dermal precursor cells have been shown to derive from the dorsomedial lip of the dermomyotome (DML). Based on its expression pattern in the DML, Wnt11 is a candidate regulator of dorsal dermis formation. Using EGFP-based cell labelling and time-lapse imaging, we show that the Wnt11 expressing DML is the source of the dense dorsal dermis. Loss-of-function studies in chicken embryos show that Wnt11 is indeed essential for the formation of dense dermis competent to support cutaneous appendage formation. Our findings show that dermogenic progenitors cannot leave the DML to form dense dorsal dermis following Wnt11 silencing. No alterations were noticeable in the patterning or in the epithelial state of the dermomyotome including the DML. Furthermore, we show that Wnt11 expression is regulated in a manner similar to the previously described early dermal marker cDermo-1. The analysis of Wnt11 mutant mice exhibits an underdeveloped dorsal dermis and strongly supports our gene silencing data in chicken embryos. We conclude that Wnt11 is required for dense dermis and subsequent cutaneous appendage formation, by influencing the cell fate decision of the cells in the DML.
脊椎动物真皮的胚胎起源可追溯到体节的生皮节、侧板中胚层和神经嵴。直接覆盖在神经管上方的真皮前体细胞呈现出独特的密集排列,并且是脊椎动物胚胎中最早诱导皮肤附属器形成的细胞。这些真皮前体细胞已被证明源自生皮节的背内侧唇(DML)。基于其在DML中的表达模式,Wnt11是背部真皮形成的候选调节因子。利用基于增强绿色荧光蛋白(EGFP)的细胞标记和延时成像技术,我们发现表达Wnt11的DML是密集的背部真皮的来源。对鸡胚进行的功能丧失研究表明,Wnt11对于形成能够支持皮肤附属器形成的致密真皮确实至关重要。我们的研究结果表明,在Wnt11沉默后,真皮形成祖细胞无法离开DML去形成密集的背部真皮。包括DML在内的生皮节的模式或上皮状态均未出现明显改变。此外,我们发现Wnt11的表达调控方式与先前描述的早期真皮标记物cDermo-1类似。对Wnt11突变小鼠的分析显示背部真皮发育不全,这有力地支持了我们在鸡胚中的基因沉默数据。我们得出结论,Wnt11通过影响DML中细胞的细胞命运决定,对于致密真皮及随后的皮肤附属器形成是必需的。