To access this work you must either be on the Smith College campus OR have valid Smith login credentials.

On Campus users: To access this work if you are on campus please Select the Download button.

Off Campus users: To access this work from off campus, please select the Off-Campus button and enter your Smith username and password when prompted.

Non-Smith users: You may request this item through Interlibrary Loan at your own library.

Publication Date


First Advisor

Michael J.F. Barresi

Document Type

Honors Project

Degree Name

Bachelor of arts


Biological Sciences


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.




vi, 75 pages : color illustrations. Includes bibliographical references (pages 63-75)