xv, 83 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / This dissertation describes research to identify genes involved in specification, patterning and development of zebrafish primary motoneurons. We first examined the spatiotemporal expression patterns of retinoic acid and retinoid X receptor mRNAs to determine whether particular ones might be involved in motoneuron specification or patterning. Retinoic acid and retinoid X receptor mRNAs are expressed at the right time to pattern motoneurons, but the expression patterns did not suggest roles for particular receptors. In contrast, netrin mRNAs are expressed in specific motoneuron intermediate targets and knockdown experiments revealed an important role in development of VaP motoneurons. Two identified motoneurons, CaP and VaP, initially form an equivalence pair. CaPs extend long axons that innervate ventral muscle. VaPs extend short axons that stop at muscle fibers called muscle pioneers; VaPs later typically die. Previous work showed that during extension, CaP axons pause at several intermediate targets, including muscle pioneers, and that both CaP and muscle pioneers are required for VaP formation. We found that mRNAs for different Netrins are expressed in intermediate targets before CaP axon contact: netrin 1a in muscle pioneers, netrin 1b in hypochord, and netrin 2 in ventral somite. We show that Netrins are unnecessary to guide CaP axons but are necessary to prevent VaP axons from extending into ventral muscle. Netrin 1a is necessary to stop VaP axons at muscle pioneers, Netrin 1a and Netrin 2 together are necessary to stop VaP axons near the hypochord, and Netrin 1b appears dispensable for CaP and VaP development. We also identify Deleted in colorectal carcinoma as a Netrin receptor that mediates the ability of Netrin 1a to cause VaP axons to stop at muscle pioneers. Our results suggest Netrins refine axon morphology to ensure final cell-appropriate axon arborization. To learn whether Netrin proteins diffuse away from their sources of synthesis to function at a distance, we are developing Netrin antibodies. If successful, the antibodies will provide the research community at large with a new tool for understanding in vivo Netrin function. This dissertation includes both my previously published and unpublished coauthored material. / Committee in charge: Monte Westerfield, Chairperson, Biology Judith Eisen, Advisor, Biology; Victoria Herman, Member, Biology; John Postlethwait, Member, Biology; Clifford Kentros, Outside Member, Psychology

La capacité remarquable des neurones et des cellules gliales à migrer collectivement sur de longues distances assure l’architecture finale du cerveau. Ce processus est extrêmement dynamique et dépend non seulement de l’interaction entre les cellules mais aussi de la présence de facteurs de transcriptions spécifiques au sein de la cellule migrante. Les protéines d’adhésion comme les cadhérines et les chimioattractants/chimiorépulsifs sont connus pour réguler et guider la migration. Si le mode d’action de ces molécules a été extensivement étudié, les cascades de signalisation qui déclenchent le chimiotropisme sont loin d’être élucidées. Au cours de mon doctorat, j’ai analysé la régulation et le rôle d’un récepteur des chimioattractant au cours de la migration de la glie. Pour ceci j’ai utilisé le modèle du développement de la chaine gliale dans l’aile de la drosophile qui représente un outil de choix pour étudier les mécanismes moléculaires régulant la migration collective. / The remarkable ability of neurons and glia to undergo long distance and collective migration ensures the final architecture and function of the brain. This is an extremely dynamic process that not only depends on cell interactions, but also on the presence of specific transcription factors in the migrating cells. Adhesion molecules such as classic cadherins and chemoattractants/repellants are known to regulate directional migration, however, how are these pathways regulated is largely unknown. While the role of these molecules controlling cell interactions has been extensively investigated, the signaling cascades that trigger chemotropism are not understood. During the course of my PhD I have analyzed the role of an adhesion molecule and the impact of a chemoattractant receptor regulated by an early transcription factor in the process. The glial chain in a developing Drosophila wing provides an excellent tool to study the molecular pathway underlying collective migration.