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Publication Date

2022-05-09

First Advisor

Michael J. F. Barresi

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Neuroscience

Keywords

commissure, axon guidance, cell guidance and migration, zebrafish, forebrain, cranial, neural crest, neuroscience, sonic hedgehog

Abstract

Cranial neural crest cells (CNCCs) are known to migrate out from the dorsal ridges of the neuroectoderm. In contrast to this conventional view, we show that reentry of CNCCs into the central nervous system (CNS) is required for proper development of the forebrain and the commissures found within. A subpopulation of these anterior CNCCs appear to re-enter the forebrain and directly contribute to both HuC/D+ and Tg(olig2:GFP)+ cell populations, and thus impact cell groups of the anterior and post optic commissures (AC and POC). We demonstrate this unusual role of CNCCs in forebrain development by observing a complete loss of NCC intfap2a/2c double mutants to show significant disruptions of both neuronal populations and forebrain commissures. As these cells were previously unseen there are little to no data on factors influencing their migration into the CNS. NCCs migrate collectively via a “chase and run” mechanism, where cells follow the SDF-1 concentration gradient secreted by the olfactory placode. However, CNCC migration could be influenced by additional cues including those secreted by CNCCs themselves. We investigate whether Sonic hedgehog (Shha), a member of the hedgehog (Hh) family of chemo attractants, is required for anterior and medial migration of NCCs (Barresi 2005, Tesla a et al 2013). Shh may function both as a mitogen and morphogen, guiding CNCCs into commissural regions of the forebrain. We visualized Sox10 positive CNCCs in the transgenic lines Tg[sox10:nls-eos] along with Tg[shha:gfp] to identify Shh expressing cells and Tg[GBS-ptch2:nls-cherry] to identify cells expressing the Shh receptor ptch2 (Hadzhiev et al, 2007). We have analyzed the impact of Shh overexpression on the forebrain and commissures by inducing heat shock in embryos from the transgenic Tg[hsp70I:shha-EGFP], and have analyzed the impact of reduced Shh function on commissure formation in embryos treated with Cyclopamine, an inhibitor of the Shh receptor Smoothened. Funded by NSF IOS-1656310.

Rights

©2022 Nadia Burnett PenkoffLidbeck. 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.

Language

English

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