Distinct Wnt members regulate the hierarchical morphogenesis if skin regioons (spinal tract) and individual feathers
Distinct Wnt members regulate the hierarchical morphogenesis if skin regioons (spinal tract) and individual feathers
复制标题
DOI：
10.1016/j.mod.2003.12.004
复制
发表时间：
2004-02-01
影响因子：
2.6
通讯作者：
Widelitz, R
中科院分区：
文献类型：
--
作者：
Chang, CH;Jiang, TX;Widelitz, R
皮肤形态发生发生在连续的阶段。首先，皮肤形成不同的区域（宏观图案化）。然后在每个区域内形成具有特定形状和大小的皮肤附属物（微图案）。异位DKK表达抑制真皮形成的羽道和个别芽，这意味着Wnt的重要性，并促使评估个别Wnt功能在不同的形态发生水平，使用羽毛模型。Wnt 1、3a、5a和11最初在整个羽道中适度表达，然后以两种方式在限制区域上调：Wnt 1和3a限制于基板上皮，然后限制于细长的远芽表皮; Wnt 5a和11分别在羽道间区域和原基间表皮或真皮中增强，然后出现在细长的远芽真皮中。它们在羽道形成中的作用是使用RCAS介导的E2/E3卵内错误表达来确定的。它们在周期性羽毛图案中的功能通过使用重建的E7皮肤外植体培养物在体外的错误表达来检查。Wnt 1降低了脊髓束的大小，但增加了羽毛原基的大小。Wnt 3a增加真皮厚度，扩大脊髓束的大小，减少interbud域间距，并产生非锥形的“巨芽”。Wnt 11和显性负性Wnt 1增强了芽间距。产生更薄的芽。在培养的真皮成纤维细胞中，Wnt 1和3a刺激细胞增殖并激活经典β-连环蛋白途径。Wnt 11抑制增殖但刺激迁移。Wnt 5a和11触发JNK通路。因此，独特的Wnt在形成真皮、束、芽间间距以及单个芽的生长和成形中具有积极和消极的作用。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Skin morphogenesis occurs in successive stages. First, the skin forms distinct regions (macropatteming). Then skin appendages with particular shapes and sizes form within each region (micropatterning). Ectopic DKK expression inhibited dermis formation in feather tracts and individual buds, implying the importance of Wnts, and prompted the assessment of individual Wnt functions at different morphogenetic levels using the feather model. Wnt 1, 3a, 5a and 11 initially were expressed moderately throughout the feather tract then were up-regulated in restricted regions following two modes: Wnt 1 and 3a became restricted to the placodal epithelium, then to the elongated distal bud epidermis; Wnt 5a and 11 intensified in the inter-tract region and interprimordia epidermis or dermis, respectively, then appeared in the elongated distal bud dermis. Their role in feather tract formation was determined using RCAS mediated misexpression in ovo at E2/E3. Their function in periodic feather patterning was examined by misexpression in vitro using reconstituted E7 skin explant cultures. Wnt 1 reduced spinal tract size, but enhanced feather primordia size. Wnt 3a increased dermal thickness, expanded the spinal tract size, reduced interbud domain spacing, and produced non-tapering 'giant buds'. Wnt 11 and dominant negative Wnt 1 enhanced interbud spacing, and. generated thinner buds. In cultured dermal fibroblasts, Wnt 1 and 3a stimulated cell proliferation and activated the canonical beta-catenin pathway. Wnt 11 inhibited proliferation but stimulated migration. Wnt 5a and 11 triggered the JNK pathway. Thus distinctive Wnts have positive and negative roles in forming the dermis, tracts, interbud spacing and the growth and shaping of individual buds. (C) 2004 Elsevier Ireland Ltd. All rights reserved.