Description
- Abstract:
- Nervous system development depends on the precise organization of a complex series of events. Many hundreds of distinct neuronal types must be generated in the correct numbers, and these neurons must then assemble into functional circuits through faithful innervation of distinct targets. Spinal commissural neurons have long served as a prime model system for studying axon guidance due to their dynamic navigation of a shared intermediate target. However, given their common guidance behavior, their molecular diversity has not been fully appreciated. Further, while many dynamic guidance mechanisms have been identified at the growth cone, transcriptional regulation remains a poorly understood aspect of dynamic regulation of guidance at intermediate targets. In Chapter 1 of this dissertation, I will introduce key concepts and molecular players in axon guidance and spinal cord development. I will then review critical steps in commissural axon guidance at the nervous system midline. Lastly, I will examine evidence for growth cone-localized and transcriptional mechanisms of dynamic guidance regulation in developing neural circuits. In Chapter 2, I will present a transcriptomic atlas of developing commissural neurons. I will characterize novel molecularly and positionally distinct subpopulations of commissural neurons and report a newly identified large-scale transcriptomic shift concomitant with midline crossing. I will also present evidence that certain crossing-associated transcriptomic changes are specific to distinct molecular subpopulations of commissural neurons. Additionally, I will elaborate on technical and methodological considerations regarding the interpretation of these data. Finally, in Chapter 3 I will contextualize key findings from Chapter 2 and propose experimental approaches to further our understanding of commissural neuron diversity and guidance.
- Notes:
- Thesis (Ph. D.)--Brown University, 2024
Citation
Abolafia, Jane Rachel,
"Gene expression programs underlying spinal commissural neuron differentiation and midline axon guidance"
(2024).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:ng8e2hek/
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....