Requirement for Shh and Fox family genes at different stages in sweat gland development (Adult)

Sweat glands play a fundamental role in thermal regulation in man, but the molecular mechanism of their development remains unknown. To initiate analyses, we compared the model of Eda mutant Tabby mice, in which sweat glands were not formed, to wild-type mice. We inferred developmental stages and critical genes based on observations at 7 time points spanning embryonic, postnatal and adult life. In wild-type footpads, sweat gland germs were detected at E17.5. The coiling of secretory portions started at postnatal day 1 (P1), and sweat gland formation was essentially complete by P5. Consistent with a controlled morphological progression, expression profiling revealed stage-specific gene expression changes. Similar to the development of hair follicles the other major skin appendage controlled by EDA sweat gland induction and initial progression was accompanied by Eda-dependent up-regulation of the Shh pathway. During the further development of sweat gland secretory portions, Foxa1 and Foxi1, not at all expressed in hair follicles, were progressively up-regulated in wild-type but not in Tabby footpads. Upon completion of wild-type development, Shh declined to Tabby levels, but Fox family genes remained at elevated levels in mature sweat glands. The results provide a framework for the further analysis of phased downstream regulation of gene action, possibly by a signaling cascade, in response to Eda. Keywords: cell type comparison design,development or differentiation design To define target genes of Eda during sweat gland development, we carried out microarray experiments with mouse footpads that from 7 developmental time points including E15.5, E16.5, E17.5, P1, P3, P5 and 8 weeks of wild-type and Tabby mice. This dataset is Adult data.汗腺在人类体温调节中发挥着基础性作用，但其发育的分子机制仍未阐明。为开展相关研究，我们将汗腺发育缺陷的外异蛋白A（Ectodysplasin A, Eda）突变Tabby小鼠模型与野生型小鼠进行了对比。基于覆盖胚胎期、出生后及成年阶段的7个时间点的观测数据，我们推断出汗腺发育的阶段划分及关键调控基因。在野生型小鼠足垫组织中，汗腺原基于胚胎第17.5天（E17.5）被检出；分泌部的卷曲形成始于出生后第1天（P1），且汗腺发育在出生后第5天（P5）基本完成。与受控的形态发生进程相符，表达谱分析揭示了阶段特异性的基因表达变化模式。与另一类受EDA调控的主要皮肤附属器——毛囊的发育过程类似，汗腺的诱导及初始发育阶段伴随有Eda依赖的音猬因子（Sonic Hedgehog, Shh）信号通路的上调激活。在汗腺分泌部的后续发育过程中，在毛囊中完全不表达的Foxa1与Foxi1基因，在野生型小鼠足垫中呈渐进式上调，而在Tabby小鼠足垫中未观察到此现象。当野生型小鼠汗腺发育成熟后，Shh的表达水平回落至Tabby小鼠的基线水平，但叉头框家族的上述基因在成熟汗腺中仍维持较高表达水平。本研究结果为解析EDA响应下、可能通过信号级联反应实现的分阶段下游基因调控机制提供了研究框架。 关键词：细胞类型比较设计、发育或分化设计 为明确汗腺发育过程中Eda的靶基因，我们针对野生型与Tabby小鼠的7个发育时间点（包括E15.5、E16.5、E17.5、P1、P3、P5及8周龄）的足垫组织开展了基因芯片（microarray）实验。本数据集为成年样本数据。