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Investigating forebrain development : robo4 cell guidance, forebrain cellular heterogeneity, and neural crest immigration
Michael J.F. Barresi
Bachelor of arts
Developmental biology, Forebrain, Zebrafish, Neural crest cells, Robo4, Cell signaling, Commissures
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 devel opment in the zebraﬁsh model system to elucidate the identity of cells at the midline that may facilitate post-optic (POC) and anterior commissure (AC) development. We have discovered that olig2+ progenitor cells occupy delineated portions of the POC and AC. We also show that Fli1a+ mesenchymal cells migrate along the pre sumptive commissure regions before and during midline axon crossing. Following mature commissures, speciﬁc blood vessels form at the midline of the POC and just ventral to and parallel to the AC. Additionally, we challenge the canonical model of zebraﬁsh forebrain development and propose that not only do a diverse population of glial cells contribute to forebrain construction, but also that cranial neural crest cells (NCCs) break convention by re-entering the central nervous system (CNS). We show that three migrating streams of NCCs exhibit diﬀerential division multiplicity while exhibiting similar physical movement. Using lineage tracing techniques and a tfap2a/tfap2c LOF neural crest deﬁcient mutant, we show that NCCs are required for forebrain development, and may give rise to HuC/D+ and olig2+ populations. Finally, we test the requirement of a cellular guidance cue, Robo4, in positioning of astroglial cells in the presumptive POC region of the forebrain, as well as for the guidance of POC axons across the diencephalic midline. To characterize the role of robo4 in forebrain development, we have created a promoterless knockout and have utilized our new computational tool, ∆SCOPE, to characterize glial and axonal fore brain phenotypes. This work begins to shed light on the diverse array of cell types and complexity of guidance mechanisms needed to build the forebrain.
2020 Mackenzie Patricia Heffernan Litz. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.
Litz, Mackenzie Patricia Heffernan, "Investigating forebrain development : robo4 cell guidance, forebrain cellular heterogeneity, and neural crest immigration" (2020). Honors Project, Smith College, Northampton, MA.
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vi, 75 pages : color illustrations. Includes bibliographical references (pages 63-75)