Wnt11 is required for oriented migration of dermogenic progenitor cells from the dorsomedial lip of the avian dermomyotome.

Wnt11 is required for oriented migration of dermogenic progenitor cells from the dorsomedial lip of the avian dermomyotome.
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DOI:
10.1371/journal.pone.0092679
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Brand-Saberi B
Brand-Saberi B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Morosan-Puopolo G;Balakrishnan-Renuka A;Yusuf F;Chen J;Dai F;Zoidl G;Lüdtke TH;Kispert A;Theiss C;Abdelsabour-Khalaf M;Brand-Saberi B

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脊椎动物真皮的胚胎起源可以追溯到体、侧板中胚层和神经嵴的真皮组织。直接覆盖在神经管上的真皮前体显示出独特的致密排列,是脊椎动物胚胎中第一个诱导皮肤附属物形成的细胞。这些真皮前体细胞已被证明起源于真皮细胞(DML)的背内侧唇。根据其在DML中的表达模式,Wnt11是背真皮形成的候选调节因子。通过基于egfp的细胞标记和延时成像,我们发现表达Wnt11的DML是致密背真皮的来源。鸡胚胎的功能缺失研究表明,Wnt11确实是致密真皮层形成所必需的,能够支持皮肤附属物的形成。我们的研究结果表明,在Wnt11沉默后,真皮源性祖细胞不能离开DML形成致密的背真皮。包括DML在内的真皮组织的模式或上皮状态未见明显改变。此外,我们发现Wnt11的表达以类似于先前描述的早期皮肤标志物cDermo-1的方式受到调节。对Wnt11突变小鼠的分析显示出一个不发达的背真皮,这有力地支持了我们在鸡胚胎中基因沉默的数据。我们得出结论,Wnt11通过影响DML中细胞命运的决定,是致密真皮层和随后的皮肤附属物形成所必需的。
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.
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