Genetic analysis of ventral motor nerve root organogenesis in zebrafish

描述（由申请人提供）：在脊椎运动神经根的发育和疾病研究中，运动轴突和雪旺细胞已被广泛研究，而神经束膜大多被忽略。由于它与这些细胞群并列，神经束膜有望在神经根器官发生和疾病中发挥不可或缺的作用。我们有一个前所未有的机会来阐明运动轴突，雪旺细胞和神经束膜之间发生的细胞-细胞相互作用，通过使用斑马鱼模型系统及其独特而强大的组合在体内延时成像和遗传学。本申请的总体目标是揭示神经束膜的起源，并随后阐明该细胞群和许旺细胞之间发生的相互作用。通过使用转基因报告，吗啉代寡核苷酸（MO）技术，药理学抑制剂和突变体，我们将证明，神经束膜是运动神经根的一个重要组成部分，并在神经根器官发生中发挥作用。最终，通过直接暗示神经束膜在神经根发育中，旨在了解许多周围神经病变（包括Charcot-Marie-Tooth病）的原因和进展的研究可以扩展到包括这种结构，并导致对这些疾病的更深入了解。

DESCRIPTION (provided by applicant): In developmental and disease studies of vertebral motor nerve roots, motor axons and Schwann cells have been extensively studied while the perineurium has been mostly ignored. Because of its juxtaposition to these cell populations, the perineurium is poised to potentially play an integral role in nerve root organogenesis and disease. We have an unprecedented opportunity to elucidate the cell-cell interactions that occur among motor axons, Schwann cells and perineurium by using the zebrafish model system and its unique and powerful combination of in vivo time-lapse imaging and genetics. The overall goal of this application is to uncover the origin of the perineurium and subsequently elucidate the interactions that occur between this cell population and Schwann cells. Through the use of transgenic reporters, morpholino oligonucleotide (MO) technology, pharmacological inhibitors and mutants, we will demonstrate that the perineurium is an essential and integral part of the motor nerve root and plays a role in nerve root organogenesis. Ultimately, by directly implicating the perineurium in nerve root development, research aimed at understanding the cause and progression of many peripheral neuropathies, including Charcot- Marie-Tooth disease, can be expanded to include this structure and lead to a deeper understanding of these disorders.