Title: Toward understanding how mossy fiber neuron diversity in the brain stem is generated
Description: Coordinated movement relies on the proper function of cerebellar and brain stem circuitry. An integral component of this circuitry is a complex of neurons in the brain stem, referred to as mossy fiber nuclei. Despite arising sequentially from the same neuroepithelium in the dorsal hindbrain, four different major subtypes of mossy fiber neurons come to reside in primarily ventral regions of the brain stem: two in the upper brain stem (pons) and two in the lower brain stem (medulla), acting to process and transfer signals to the cerebellum from the cerebral cortex and spinal cord, respectively. Thus, mossy fiber neurons differ not only in their topographical locations in the brain stem, but also by the unique function served through neuron action at each location. How these topographical and functional differences are established during development remains largely unknown. The studies conducted during the course of this dissertation were part of a larger effort toward understanding how such a diverse population of neurons is generated and distributed from the same germinal zone in the dorsal hindbrain, the hindbrain rhombic lip. Here, using a variety of genetic, embryological and molecular approaches, we extend our knowledge base in three directions. (1) We show that mossy fiber progeny cells emigrate from the same pool of progenitor cells localized to a precise positional coordinate along the dorsoventral (DV) and rostrocaudal (RC) axes of the hindbrain rhombic lip--this positional coordinate is Math1 :rhomomeres 6-8. (2) We find that temporal changes in gene expression within this progenitor cell population correlates with the production of the individual subtypes of mossy fiber brainstem neurons.

It is possible that such changes in gene expression are responsible for the sequential production of each subtype. (3) We demonstrate that the transcription factor, Zic1 , influences two properties of mossy fiber neuron development: where the neuron settles in the brain stem and to which cerebellar hemisphere is projects. Together, the studies presented in this dissertation are important first steps toward a greater understanding of how mossy fiber neuron diversity in the brainstem is generated.