【摘要】：毛囊是具有周期性生長特征的、復(fù)雜的微器官。在胚胎發(fā)育時期,毛囊起始于表皮細(xì)胞和間充質(zhì)細(xì)胞的相互作用。當(dāng)上皮細(xì)胞向下增殖并進(jìn)入真皮時,毛母質(zhì)細(xì)胞會包繞作為主要信號源的真皮乳頭細(xì)胞,并且增殖分化為具有多層結(jié)構(gòu)的內(nèi)根鞘和毛干。其中內(nèi)根鞘由亨勒層,郝胥黎層和鞘小皮組成。毛干也由三層結(jié)構(gòu)組成,依次為毛小皮,皮質(zhì)和髓質(zhì)。毛干最內(nèi)層的角質(zhì)層與內(nèi)根鞘的角質(zhì)層相互咬合,形成一種錨定結(jié)構(gòu)。這種結(jié)構(gòu)能夠有效地防止毛干的脫落。毛囊分化的調(diào)控涉及多條信號通路,包括Bmp,homeobox基因以及Wnt。這些信號在真皮乳頭或毛母質(zhì)細(xì)胞中的特異性表達(dá)決定了它們在分化中的作用。然而,人們對于其中涉及的細(xì)胞和分子機(jī)制仍然知之甚少。 Gsdma3基因是近年來新發(fā)現(xiàn)的小鼠基因,被認(rèn)為是一個突變熱點。之前的研究認(rèn)為,作為一個突變位點,Gsdma3的突變會導(dǎo)致小鼠產(chǎn)生脫毛以及過度角化的表型。已有研究都顯示了Gsdma3在毛囊維持上起著重要作用。然而,為什么Gsdma3突變鼠會脫毛,其中又涉及了哪些調(diào)控機(jī)制,對于這些問題我們還不清楚。先前的研究分別通過原位雜交和免疫組織化學(xué)顯示了Gsdma3 mRNA和蛋白的表達(dá),但結(jié)果卻并不一致。 為了查證Gsdma3的缺失是如何導(dǎo)致毛發(fā)缺陷的,我們把一種新的Gsmda3突變鼠作為我們的實驗?zāi)Ｐ�。在這些突變鼠中,外部毛發(fā)變短并且參差不齊。在出生后25天,小鼠就開始從頭部區(qū)域開始脫毛,直至整個背部。但是,當(dāng)一個新的毛囊周期開始時,毛發(fā)也會重新生長。這個過程伴隨漸進(jìn)性的毛發(fā)脫落和生長。超微結(jié)構(gòu)和組織學(xué)分析顯示,該突變鼠的毛發(fā)結(jié)構(gòu)異常,角蛋白表達(dá)減少。錨定結(jié)構(gòu)的丟失和異常的結(jié)構(gòu)蛋白表達(dá)都提示了毛發(fā)不能錨定在毛囊中,并且難以抵抗外力。因此,Gsdma3的功能缺失會使內(nèi)根鞘和毛干結(jié)構(gòu)分化異常。我們用免疫組織化學(xué)檢測了Gsdma3表達(dá)于毛母質(zhì),內(nèi)根鞘以及毛干,而這些細(xì)胞類型都與毛囊分化密切相關(guān)。Gsdma3缺陷的分子分析顯示,Msx2調(diào)控通路的主要調(diào)控子在突變鼠中顯著下調(diào)。并且Gsdma3與Msx2的表達(dá)部位一致。當(dāng)我們通過皮下質(zhì)粒注射過表達(dá)Gsdma3的時候,所有這些基因的表達(dá)又會上調(diào)。這些結(jié)果顯示了Gsdma3可能直接或間接調(diào)控Msx2信號通路。總之,我們的結(jié)果提示Gsdma3對于毛囊分化至關(guān)重要,且可能是通過調(diào)控Msx2/Foxn1/acidic hair keratin信號級聯(lián)來起作用的。
[Abstract]:Hair follicles are complex microorgans characterized by periodic growth. During embryonic development, hair follicles begin with the interaction of epidermal cells and mesenchymal cells. When the epithelial cells proliferate downward and enter the dermis, the dermal papilla cells, which are the main signal sources, will be wrapped around the hair mother cells, and they will proliferate and differentiate into the inner root sheath and the hair stem with multilayer structure. The inner root sheath consists of Henley layer, Huxley layer and sheath skin. The hair stem is also composed of three layers, which are the trichomes, cortex and medulla. The cuticle of the innermost layer of the hair stem bites with the cuticle of the inner root sheath to form an anchor structure. This structure can effectively prevent the hair from falling off. Regulation of hair follicle differentiation involves multiple signaling pathways, including Bmp,homeobox gene and Wnt. The specific expression of these signals in dermal papilla or dermal mother cells determines their role in differentiation. However, little is known about the cellular and molecular mechanisms involved. Gsdma3 gene is a newly discovered mouse gene in recent years, which is considered to be a hot spot of mutation. Previous studies have suggested that mutations in Gsdma3, as a mutation site, lead to hair loss and hyperkeratosis in mice. Previous studies have shown that Gsdma3 plays an important role in hair follicle maintenance. However, it is not clear why Gsdma3 mutant mice lose hair and what regulatory mechanisms are involved. Previous studies showed the expression of Gsdma3 mRNA and protein by in situ hybridization and immunohistochemistry, but the results were not consistent. In order to find out how the loss of Gsdma3 leads to hair defects, we used a new Gsmda3 mutant mouse as our experimental model. In these mutant mice, the outer hair is shorter and uneven. At 25 days after birth, the mouse began hair removal from the head area to the entire back. However, when a new hair follicle cycle begins, the hair also grows again. This process is accompanied by progressive hair loss and growth. Ultrastructural and histological analysis showed that the hair structure of the mutant mouse was abnormal and the expression of keratin decreased. Loss of anchoring structure and abnormal expression of structural protein indicate that hair can not be anchored in hair follicles and can not resist external force. Therefore, the absence of Gsdma3 function may cause abnormal differentiation of inner root sheath and hairy stem structure. We used immunohistochemistry to detect the expression of Gsdma3 in hair matrix, inner root sheath and hair stem, and these cell types were closely related to hair follicle differentiation. The main regulators of the Msx2 regulatory pathway were significantly down-regulated in mutant mice. The expression of Gsdma3 and Msx2 were consistent. When we express Gsdma3 subcutaneously, all these genes are up-regulated. These results suggest that Gsdma3 may directly or indirectly regulate the Msx2 signaling pathway. In conclusion, our results suggest that Gsdma3 is essential for hair follicle differentiation and may function by regulating Msx2/Foxn1/acidic hair keratin signaling cascades.
【學(xué)位授予單位】：重慶大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R751

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相關(guān)期刊論文 前1條

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本文編號：2302982