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Author ORCID Identifier

https://orcid.org/0000-0002-7999-169X

AccessType

Campus-Only Access for Five (5) Years

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2021

Month Degree Awarded

February

First Advisor

Michael JF Barresi

Second Advisor

Gerald Downes

Third Advisor

Abigail Jensen

Fourth Advisor

Jesse Mager

Subject Categories

Cell Biology | Developmental Biology | Developmental Neuroscience | Molecular and Cellular Neuroscience | Molecular Biology

Abstract

During embryonic development of bilateral organisms, neurons send axons across the midline at specific points to connect the two halves of the nervous system with a commissure. Little is known about the cells at the midline that facilitate this tightly regulated process. We exploit the conserved process of vertebrate embryonic development in the zebrafish model system to elucidate the identity of cells at the midline that may facilitate postoptic (POC) and anterior commissure (AC) development. To facilitate this investigation, we developed a suite of Python modules to analyze the relationships between the commissural architecture and the forebrain commissures. We have shed light on the progression of commissural architecture condensation and show that the repellent guidance cues, Slit-Robo, shape the forebrain architecture and the forebrain commissures. Further investigation of the cellular contributions to the zebrafish forebrain show that three different gfap+ astroglial cell morphologies persist in contact with pathfinding axons throughout commissure formation. Similarly, olig2+ progenitor cells occupy delineated portions of the postoptic and anterior commissures. We conclude that gfap+ and olig2+ progenitor cells give rise to neuronal populations in both the telencephalon and diencephalon. Interestingly, these varied cell populations showed significant developmental heterochrony between the telencephalon and diencephalon. We also showed that fli1a+ mesenchymal cells migrate along the presumptive commissure regions before and during midline axon crossing. These investigations also revealed neural crest contributions to the anterior of the embryo. Excitingly, through use of a tfap2a/tfap2b LOF NCC mutant we discovered a novel requirement for neural crest cells in zebrafish forebrain development where their appropriate migration into the forebrain is required for appropriate commissure spacing and axon guidance. Subsequent investigations of NCC requirement and forebrain contributions utilizing lineage tracing techniques and live cell tracking have shown that NCCs break convention by re-entering the CNS. These same NCCs then contribute to forebrain neuronal populations. Ultimately, by unraveling the coordinated efforts of migrating neural crest, neural progenitors, and glial cells that construct the relatively simple zebrafish forebrain, we can provide insight into potentially conserved mechanisms underlying brain development and disease.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

Available for download on Tuesday, February 01, 2022

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