COBRE: CREIGHTON UNIVERISTY: P1:ROLE OF MICRORNAS IN DEVELOPMENT OF THE EAR

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 周围神经系统（PNS）的感觉和运动成分的发育受到复杂的信号分子网络的严格调节。这些信号分子控制细胞过程，如细胞迁移、增殖、分化、命运特化、轴突引导和特定突触的建立。在中枢神经系统中，通过erbB家族成员（包括表皮生长因子受体（EGFR））的信号转导影响神经胶质和神经元的增殖、分化、命运获得、神经突生长和存活。EGFR的缺失导致CNS中神经元迁移缺陷以及皮肤上皮的异常增殖、分化和维持。通过EGFR家族成员的信号转导，所有这些都在PNS中表达，对于运动和感觉神经元的正常发育至关重要。该提议旨在检验EGFR信号传导也是外周神经系统正常发育所需的假设，以及神经细胞和靶细胞之间的相互作用调节PNS发育的假设。具体目标1. 通过使用EGFR纯合子缺失小鼠检查发育期间EGFR缺失对皮肤神经支配的影响，确定EGFR在PNS发生中的作用。具体目标2。 确定EGFR对PNS的发育调节是细胞自主的还是受靶组织中EGFR表达的调节。具体目标3。确定EGFR调控PNS发生的下游效应基因。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The development of the sensory and motor components of the peripheral nervous system (PNS) is tightly regulated by a complex network of signaling molecules. These signaling molecules control cellular processes such as cell migration, proliferation, differentiation, fate specification, axon guidance, and the establishment of specific synapses. In the central nervous system, signal transduction through members of the erbB family, including the epidermal growth factor receptor (EGFR), influences glial and neuronal proliferation, differentiation, fate acquisition, neurite outgrowth, and survival. Loss of EGFR results in defective neuronal migration in the CNS as well as abnormal proliferation, differentiation, and maintenance of the cutaneous epithelium. Signal transduction through EGFR family members, all of which are expressed in the PNS, is vital for normal development of both motor and sensory neurons. This proposal is designed to test the hypotheses that EGFR signaling is also required for proper development of the peripheral nervous system and that interactions between neural and target cells regulate PNS development. Specific aim 1. To determine the role of EGFR in the development of the PNS by examining the effects of loss of EGFR on innervation of the skin during development using EGFR homozygous null mice. Specific aim 2. To determine whether developmental regulation of the PNS by EGFR is cell autonomous or regulated by the expression of EGFR in the target tissue. Specific Aim 3. To identify downstream effector genes through which EGFR regulates the development of the PNS.