Differentiation and patterning of cells originating in the zebrafish neuroectoderm

Abstract

Vertebrate nervous system development requires a complex series of events to transform a flat neuroepithelium into complex structures containing specialized cell types. The anterior neuroectoderm gives rise to the brain and is the origin for some of the first neurons that differentiate. It is also the origin of the cranial neural crest cells that form craniofacial features. This thesis focuses on the embryonic development of two tissues that arise from the zebrafish anterior neuroectoderm, the epithalamus, a region of the dorsal forebrain, and the mandible, the lower jaw. Early in development, the flat neural plate folds into a neural tube. The pineal gland, an organ involved with circadian rhythms, begins as two precursor domains at the lateral edges of the neural plate that converge into a single tissue when the neural tube closes. The pineal gland, along with the parapineal gland and habenula nuclei, form the epithalamus in the dorsal forebrain. In embryos with open neural tubes, the left and the right sides of the pineal and surrounding epithalamus are widely spaced. I found that despite this displacement, pineal cell types differentiate normally and initiate their rhythmic function. Conversely left-right asymmetry in the epithalamus was lost; both sides exhibited left-sided characteristics. Further, this loss of asymmetry in the epithalamus was correlated to severity in neural tube defects. Embryos with left isomerism had significantly wider pineal anlage domains than those with normal or reversed asymmetry. Cranial neural crest cells from the dorsal neural tube migrate to form craniofacial structures, including the cartilaginous precursor to the mandible, Meckel's cartilage. The bigtime (bti) mutant exhibits reductions in mandibular development. I found that although cranial neural crest cells localize normally to the lower jaw region in these mutants, they fail to differentiate into functional chondrocytes that secrete a sufficient amount of collagenous extracellular matrix.