Molecular Control of Reticulospinal Neuron Development

这项研究将在墨西哥进行，作为NIH Grant NS37116的延伸。 后脑网状脊髓神经元参与脊髓的调制 内脏和躯体运动反应，如保持姿势和 心血管和呼吸功能的控制。两大集团 在哺乳动物的脑干中已经描述了网状脊髓神经元，其中之一 脑桥和另一个在延髓。这些群体在方式上是不同的 它们投射到脊髓(同侧的腹索和 分别位于两侧侧索中)和它们的末端 部位(脑桥纤维在脊髓中终止的腹侧比 有髓的)。导致这些疾病发生的分子过程 和其他在形态和生理上可区分的网状脊髓 然而，神经元亚型仍有待阐明。这样做的具体目的是 提案解决了两个主要问题。首先，不同的子类型是否可以 根据转录因子和转录因子定义网状脊髓神经元 神经递质的表达？第二，这些因素是否在功能上可以预测 身份和轴突投射途径？为了回答这些问题，荧光 逆行标记将首先与原位标记结合使用 杂交和免疫染色检测LIM同源结构域的表达 和其他转录因子在网状脊髓神经元亚型中的表达。一个 类似的策略将被用来定义它们的神经递质表型。 第二，将采用显性-负性形式的核LiM交互作用 阻断LIM同源结构域功能，从而研究这些 因素在网状脊髓发育中发挥作用。第三，异位表达 正在研究中的转录因子将通过体内电穿孔获得 评价其在网状脊髓轴突投射中的作用。 获得这些问题的答案将有助于更好地理解 网状脊髓神经元特性和轴突的分子决定因素 寻路。这反过来将有助于研究设立 复杂的马达电路。通过这些努力，可能会出现恢复 因受伤或疾病而丧失的运动控制功能。

This research will be done in Mexico as an extension of NIH Grant NS37116. Hindbrain reticulospinal neurons are involved in the modulation of spinal visceral and somatic motor responses such as maintenance of posture and the control of cardiovascular and respiratory functions. Two large groups of reticulospinal neurons have been described in the mammalian brainstem, one in the pons and the other in the medulla. These groups are dissimilar in the way they project into the spinal cord (ipsilaterally in the ventral funiculus and bilaterally in the lateral funiculus, respectively) and in their termination sites (pontine fibers terminating more ventrally in the spinal cord than do the medullary ones). The molecular processes underlying the development of these and other morphologically and physiologically distinguishable reticulospinal neuron subtypes, however, remains to be elucidated. The specific aims of this proposal address two major questions. First, can the different subtypes of reticulospinal neurons be defined on the basis of the transcription factors and neurotransmitters expressed? Second, do these factors functionally predict identity and axonal projection pathway? To answer these questions, fluorescent retrograde labeling will first be used in combination with in situ hybridization and immunostaining to determine the expression of LIM homeodomain and other transcription factors in the subtypes of reticulospinal neurons. A similar strategy will be employed to define their neurotransmitter phenotype. Second, a dominant-negative form of the nuclear LIM interactor will be employed to block LIM homeodomain function and thus to investigate the role these factors play in reticulospinal development. Third, ectopic expression of the transcription factors under study will be attained by in ovo electroporation in chick hindbrain to assess its effect in reticulospinal axon projection. Obtaining the answers to these questions will lead to a better understanding of the molecular determinants of reticulospinal neuron identity and axonal pathfinding. This will, in turn, facilitate the study of the establishment of complex motor circuits. From these efforts, procedures might emerge to restore motor control functions lost by injury or disease.