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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 周围神经系统(PNS)的感觉和运动成分的发育受到一个复杂的信号分子网络的严格调控。这些信号分子控制细胞过程，如细胞迁移、增殖、分化、命运指定、轴突引导和特定突触的建立。在中枢神经系统中，通过包括表皮生长因子受体(EGFR)在内的erbB家族成员的信号转导，影响神经胶质细胞和神经元的增殖、分化、命运获得、轴突生长和存活。EGFR的缺失会导致中枢神经系统神经元迁移障碍，以及皮肤上皮细胞的异常增殖、分化和维持。通过EGFR家族成员的信号转导对于运动神经元和感觉神经元的正常发育都是至关重要的。这一建议旨在检验这样的假设，即EGFR信号对周围神经系统的正常发育也是必需的，以及神经和靶细胞之间的相互作用调节PNS的发育。具体目的1.利用EGFR纯合子缺失小鼠检测EGFR缺失对发育过程中皮肤神经支配的影响，以确定EGFR在PNS发生发展中的作用。具体目的2.确定EGFR对三叉神经节发育的调节是细胞自主的，还是受靶组织中EGFR表达的调节。具体目的3.确定EGFR调控三叉神经节发育的下游效应基因。

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.