Function of Engrailed-1 in eccrine gland development

描述(申请人提供)：这项研究的目标是确定小汗腺形成的机制，最终目的是在受损的皮肤或体外产生的皮肤移植物中再生小汗腺。虽然EN-1在外胚层中的表达与小鼠外分泌腺的发育有关，但由于EN-1活性对汗腺所在的腹侧肢体的正常发育的重叠要求，使得EN-1在外分泌腺发育中的直接作用与在确定腹侧身份方面的间接作用相分离。最近，我们获得了更多证据，表明EN-1在内分泌发育中起着直接作用。我们将使用可诱导的转基因模型和一种新的体外分泌腺发育实验来分析这一功能，以测试EN-1表达在调节分泌腺发育中的功能。这种效应的机制将通过分离表皮中的直接效应和对底层真皮诱导特性的间接效应来剖析。成功完成这些目标将确定EN-1的功能，并开发一个有效的体外分析内分泌腺发育的平台。这项工作的终点分析是外分泌腺的体外发育，因此为外分泌腺在皮肤等效物中的再生提供了直接的见解。

DESCRIPTION (provided by applicant): The goal of this research is to identify the mechanisms by which eccrine glands are formed with the ultimate aim of regenerating eccrine glands in damaged human skin or in vitro generated skin grafts. Although the expression of En-1 in the ectoderm has been implicated in eccrine gland development in the mouse, the overlapping requirement of engrailed-1 activity for the normal development of the ventral limb in which sweat glands are found has precluded separation of a direct role for En-1 in eccrine gland development from an indirect role in specifying ventral identity. Recently we have generated additional evidence that En-1 plays a direct role in eccrine development. We will dissect that function using an inducible transgenic model and a novel in vitro eccrine gland development assay to test the function of En-1 expression in regulating eccrine gland development. The mechanisms of this effect will be dissected by separating direct effects in the epidermis from indirect effects on the inductive properties of the underlying dermis. Successful completion of these aims will identify the function of En-1 and develop a platform for efficient in vitro analysi of eccrine gland development. The endpoint assay in this work is the in vitro development of eccrine glands, and as such provides direct insight to regeneration of eccrine glands in skin equivalents.