Post Transcriptional Regulation of Trophoblast Differentiation

早期胚胎的着床需要成熟的胚胎滋养外胚层之间的相互作用 和母体子宫内膜。这就需要对差异化的精细控制和 两张纸巾。试点项目II的总体目标是剖析microRNA在转录后调控中的作用， 滋养层分化的调节。该试点是一个为期两年的合作项目， 滋养层分化、着床和早期胚胎发育中心的成员和核心， 发展为了解决该项目的总体目标，一个基因模型，专门敲除 microRNA的功能已经被开发出来。该模型将用于表型表征 滋养层决定、分化和功能中的miRNA。补助金的具体目的包括：1） 微RNA在植入前发育中的作用的表征。这将包括他们的作用， 最早的细胞命运选择定义了滋养外胚层与上胚层，以及microRNA在滋养外胚层中的作用。 产生能够与母体子宫内膜附着和接触的健康胚泡。（二） 微RNA在滋养外胚层发育后期的作用的表征， 滋养层干细胞的维持和分化以及敲除滋养外胚层的能力 通过子宫内膜基质侵入和迁移。这项工作将使用条件性microRNA敲除 该实验室开发的模型使我们能够绕过过早发育造成的早期缺陷， miRNAs的丢失这一目标也将确定整个过程中microRNA的差异表达。 滋养外胚层发育。该试验项目将作为未来实验和R01型的跳板。 赠款了解由miRNAs调控的特定发育途径，然后使用 诊断和治疗，以跟踪和治疗胚胎植入缺陷的患者。 microRNA是一种新发现的细胞调节因子，其在细胞内的普遍性和全局性影响， 基因功能表明它们在正常和异常的人类发育中起着核心作用。这 已经证实了癌症等疾病，并且可能会在生殖疾病中出现这种情况， 好.这项试点资助的完成将为microRNA在正常人中的作用提供初步的见解。 生殖发育所需的解剖他们的作用，以及确定潜在的诊断和 生殖疾病的治疗靶点。

Implantation of the early embryo requires the interaction between the maturing embryonic trophectoderm and maternal endometrium. This requires exquisite control of differentiation and communication between the two tissues. The overall goal of pilot project II is to dissect the role of microRNAs in the post-transcriptionnal regulation of trophoblast differentiation. This pilot is a two year collaborative project based on the expertise of the members and cores of the proposed center for trophoblast differentiation, implantation, and early development. To address the overall goal of the project, a genetic model that specifically knocks-out microRNA function has been developed. This model will be used to phenotypically characterize the role of miRNAs in trophoblast determination, differentiation, and function. The specific aims of the grant include: 1) characterization of the role of microRNAs in pre-implantation development. This will include their role in earliest cell fate choice defining the trophectoderm versus the epiblast as well the role of microRNAs in the producing a healthy blastocyst that is able to attach and interface with the matenal endometrium. 2) characterization of the role of microRNAs in later stages of trophectoderm development including the maintenance and differentiation of trophoblast stem cells as well as the capacity of knockout trophectoderm to invade and migrate through the endometrial matrix. This work will use a conditional microRNA knockout model that the lab has developed enabling us to bypass earlier defects in development caused by premature loss of miRNAs. This aim will also determine the differential expression of microRNAs throughout trophectoderm development. This pilot project will act as a springboard to future experiments and R01-type grants aimed at understanding specific developmental pathways regulated by miRNAs, which then be used diagnostically and therapeutically to follow and treat patients with defects in embryonic implantation. MicroRNAs are a newly discovered class of cell regulators whose pervasiveness and global effects on gene function suggests they have a central role in both normal and abnormal human development. This has already been borne out for diseases such as cancer and likely will be the case in reproductive disease as well. Completion of this pilot grant will provide initial insights into the role of microRNAs in normal reproductive development necessary to dissect their role as well as identify potential diagnostic and therapeutic targets in reproductive disease.