Regulation and Function of Hox Proteins in Zebrafish Hindbrain Patterning

脊椎动物的大脑包含数十亿个神经元，分为无数专门的角色。在胚胎发生过程中，最关键的事件之一是独特的神经元亚型的分化，促进适当的细胞迁移，轴突寻路和神经递质合成。然而，经过几十年的研究，指定神经元亚型的机制并不完全清楚。脊椎动物后脑的颅运动神经元集群代表了一个强大的模型来解决这个关键问题。后脑暂时分为一系列谱系限制的隔间，称为菱形节。每个菱形节段包含一组独特的神经元。我们的研究计划重点是指定的身份的菱形4（r4），这是在后脑内的中央信号中心的机制。在我们实验室进行的实验表明，有三个关键的调节后脑r4的身份。我们实验室的实验涉及Pbx，Hox-1，Fgf和视黄酸在指定适当的菱形4身份。这项研究计划将使用两个项目来研究这一途径，并确定建立后脑信号中心的分子机制。

The vertebrate brain contains billions of neurons, divided into a myriad of specialized roles. During embryogenesis, one of the most critical events is the differentiation of unique neuronal subtypes, facilitating proper cell migration, axon pathfinding, and neurotransmitter synthesis. Yet, after decades of study, the mechanisms specifying neuronal subtype are incompletely understood. The clustered cranial motor neurons of the vertebrate hindbrain represent a powerful model to address this critical question. The hindbrain is transiently divided into a series of lineage-restricted compartments, which are known as rhombomeres. Each rhombomere segment contains a unique group of neurons. Our research program focus is on the mechanisms that specify the identity of rhombomere 4 (r4), which is the central signaling center within the hindbrain. Experiments done in our laboratory have implicated three key regulators of hindbrain r4 identity. Our lab's experiments implicate Pbx, Hox-1, Fgf, and retinoic acid in specifying proper rhombomere 4 identity. This research proposal will use two projects to investigate this pathway and determine the molecular mechanisms underlying the establishment of the hindbrain signaling center.