Analysis of Spatial & Temporal Dependence of Rhombic Lip Derivatives on Math1

后脑发育中断与多种人类疾病有关，这些疾病会导致显著的 发病率和死亡率，如Chiari畸形、婴儿猝死综合症和自闭症。《数学》 基因编码一种基本的螺旋-环-螺旋转录因子，其功能是产生 发育中的后脑有多种神经元亚型，包括那些参与呼吸控制的亚型。我的 该提案旨在了解Mathl如何促进正常的后脑发育，以努力更好地 了解导致人类严重神经发育状况的精神错乱。 我的目标是确定空间和时间线索如何指定MafM-Line细胞的细胞命运 从菱形嘴唇衍生而来。该项目的具体目标是1)扰乱数学1在空间上的功能- 限定各种菱形唇形衍生品的原产地；2)确定 MA#77-线状细胞的起源；以及3)根据时间选择性地消除Mathl依赖的细胞群体 起源。我将使用条件性基因敲除系统来测试一个假设，即在一个空间-或 时间依赖的方式会导致特定神经元亚群的缺失，导致不同的表型 取决于受影响的细胞组。这一策略将允许我构建一个空间和 小鼠菱形嘴唇的时间命运图，精确定位呼吸控制所必需的神经元，并评估 由于后脑特定神经元亚群的丧失而导致的生理和行为后果。 我的整个职业目标是成为一名独立的医生/科学家，专注于理解 先天神经异常。我将把我的大部分时间花在基础研究上 实验室，但我也会看到一组精选的脑畸形患者。我的最终目标是 描述和识别导致这些异常的基因，希望能更好地 了解是什么导致了它们，以及如果可能的话，可以如何有效地预防或治疗它们。 贝勒医学院为我的成功提供了完美的环境。我的导师胡达·佐格比博士 是一位国际知名的内科医生/科学家，有着丰富的培训记录。各部门对 我的研究生涯，与科学咨询委员会的互动，以及在贝勒和 其他地方也会帮助我实现我的目标。

Disruptions of hindbrain development are implicated in multiple human disorders that cause significant morbidity and mortality such as Chiari malformations, sudden infant death syndrome and autism. The Mathl gene encodes a basic helix-loop-helix transcription factor whose function is necessaryfor the creation of multiple neuronal subtypes in the developing hindbrain, including those involved in breathing control. My proposal seeks to understand how Mathl contributes to normal hindbrain development in an effort to better understand derangements that cause serious neurodevelopmental human conditions. My goal is to determine how spatial and temporal cues specify the cellular fates of MafM-lineal cells derived from the rhombic lip. The specific aims of the project are to 1) disrupt Math1function in a spatially- restricted manner to define the sites of origin of various rhombic lip derivatives; 2) determine the time of origin of Ma#77-lineal cells; and 3) selectively eliminate Mathl-dependent cell populations based on time of origin. I will use conditional knockout systemsto test the hypothesis that disruption of Mathl in a spatial- or time-dependent manner causes deletion of specific subsets of neurons, resulting in different phenotypes depending on the cell groups that are affected. This strategy will allow me to construct a spatial and temporal fate map of the murine rhombic lip, pinpoint neurons essential for breathing control, and evaluate physiological and behavioral consequences resulting from loss of specific neuronal subsets in the hindbrain. My overall career goal is to become an independent physician/scientist who focuses on understanding congenital neurological abnormalities. I will spend the majority of my time running a basic research laboratory, but I will also see a select group of patients with brain malformations. My ultimate goal is to characterize and identify genes that are responsible for these abnormalities in the hopes of better understanding what causes them and how they may be effectively prevented or treated, if possible. Baylor College of Medicine provides the perfect environment for my success. My mentor, Dr. Huda Zoghbi, is an internationally known physician/scientist with a tremendous training record. Departmental support of my research career, interaction with a Scientific Advisory Committee, and formal coursework at Baylor and elsewhere will also help me to achieve my goals.