Cui Chang-Yi, Yin Mingzhu, Sima Jian, Childress Victoria, Michel Marc, Piao Yulan, Schlessinger David
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Development. 2014 Oct;141(19):3752-60. doi: 10.1242/dev.109231.
To maintain body temperature, sweat glands develop from embryonic ectoderm by a poorly defined mechanism. We demonstrate a temporal cascade of regulation during mouse sweat gland formation. Sweat gland induction failed completely when canonical Wnt signaling was blocked in skin epithelium, and was accompanied by sharp downregulation of downstream Wnt, Eda and Shh pathway genes. The Wnt antagonist Dkk4 appeared to inhibit this induction: Dkk4 was sharply downregulated in β-catenin-ablated mice, indicating that it is induced by Wnt/β-catenin; however, its overexpression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt. Wnt signaling was still active and nascent sweat gland pre-germs were still seen in Eda-null mice, but the pre-germs failed to develop further and the downstream Shh pathway was not activated. When Wnt and Eda were intact but Shh was ablated, germ induction and subsequent duct formation occurred normally, but the final stage of secretory coil formation failed. Thus, sweat gland development shows a relay of regulatory steps initiated by Wnt/β-catenin - itself modulated by Dkk4 - with subsequent participation of Eda and Shh pathways.
为维持体温，汗腺由胚胎外胚层通过一种尚不明确的机制发育而来。我们展示了小鼠汗腺形成过程中的一个时间性调控级联。当皮肤上皮中的经典Wnt信号被阻断时，汗腺诱导完全失败，并伴随着下游Wnt、Eda和Shh信号通路基因的急剧下调。Wnt拮抗剂Dkk4似乎抑制这种诱导：Dkk4在β-连环蛋白缺失的小鼠中急剧下调，表明它是由Wnt/β-连环蛋白诱导的；然而，其过表达抑制Wnt靶基因并显著减少腺体数量。Eda信号在Wnt之后起作用。在Eda基因缺失的小鼠中，Wnt信号仍然活跃且仍可见新生汗腺前体，但前体未能进一步发育且下游Shh信号通路未被激活。当Wnt和Eda完整但Shh被敲除时，胚芽诱导和随后的导管形成正常发生，但分泌盘形成的最后阶段失败。因此，汗腺发育显示出由Wnt/β-连环蛋白启动（其自身受Dkk4调节）、随后Eda和Shh信号通路参与的一系列调控步骤。
