β-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse
β-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse
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DOI：
10.1016/j.ydbio.2006.04.449
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发表时间：
2006-08-01
影响因子：
2.7
通讯作者：
Conlon, Ronald A.
中科院分区：
文献类型：
--
作者：
Atit, Radhika;Sgaier, Sema K.;Conlon, Ronald A.
背侧真皮和外轴肌已被证明起源于雏鸡的中央皮肌节。EN1是一种同源异型盒转录因子基因，在中央皮肌体中表达。我们通过在小鼠中的遗传命运午睡表明，中央皮肌节中表达EN1的细胞产生背侧真皮和外轴肌肉，并且出人意料地产生肩部间的棕色脂肪。因此，表达EN1的中央皮肌节通常在小鼠身上产生三种不同的命运。Win信号在皮肤肌节发育的早期阶段很重要，但决定皮肤命运的信号尚未确定。利用报告基因进行Win信号转导，我们发现表达EN1的细胞直接位于外胚层表面之下，转导Wnt信号。当必需的Wnt转导因子β-catenin在EN1细胞中发生突变时，它会导致表达Dermo1的背部真皮祖细胞和真皮的丧失。相反，当β-连环蛋白在EN1细胞中被激活时，它会在EN1区域的所有细胞中诱导Dermo1的表达，并扰乱肌肉基因的表达。我们的结果表明，小鼠中央皮肌节产生真皮、肌肉和棕色脂肪，写字信号通常指示细胞选择背部真皮命运。(C)2006 Elsevier Inc.保留所有权利。
Dorsal dermis and epaxial muscle have been shown to arise from the central dermomyotome in the chick. En1 is a homeobox transcription factor gene expressed in the central dermomyotome. We show by genetic fate nnapping in the mouse that En1-expressing cells of the central dermomyotome give rise to dorsal dermis and epaxial muscle and, unexpectedly, to interscapular brown fat. Thus, the En1-expressing central dermomyotome normally gives rise to three distinct fates in mice. Win signals are important in early stages of dermomyotome development, but the signal that acts to specify the dermal fate has not been identified. Using a reporter transgene for Win signal transduction, we show that the En1-expressing cells directly underneath the surface ectoderm transduce Wnt signals. When the essential Wnt transducer beta-catenin is mutated in En1 cells, it results in the loss of Dermo1-expressing dorsal dermal progenitors and dermis. Conversely, when beta-catenin was activated in En1 cells, it induces Dermo1-expression in all cells of the En1 domain and disrupts muscle gene expression. Our results indicate that the mouse central dermomyotome gives rise to dermis, muscle, and brown fat, and that Writ signalling normally instructs cells to select the dorsal dermal fate. (c) 2006 Elsevier Inc. All rights reserved.