My thesis work concentrated on organogenesis in zebrafish. Although the most proliferative studies focused on apicobasal cell polarity and neurulation, I also researched additional topics including pancreas and heart organogenesis. The majority of this work originated from a forward genetic screen using Tg(gutGFP)s854 zebrafish. This screen generated several mutants, three of which I have characterized and identified the causative molecular lesion.
In Chapters 2 and 3, I discuss one mutant, pard6gammab. These mutants affect one component of a multi-protein complex regulating apicobasal polarity, the Par3/Par6/aPKC complex. The pard6gammab mutant represents the first mutation of this protein in a vertebrate system, and has helped reveal the functional diversity of the Par6 protein family in vertebrates. pard6gammab mutants show phenotypes in epithelial tissues as well as a novel phenotype in the development of the neurocoel.
In Appendix 1, I discuss preliminary research on another mutant, prpf18s490, that affects a component of the spliceosome. This mutant provides an in vivo system to study splicing in vertebrates. Appendix 2 outlines research I have performed on an allele of the yng/smarca4 mutation, which affects a protein involved in chromatin remodeling. These mutants have ectopic Islet-expressing cells outside of the pancreas region. To determine what causes this phenotype, I investigated a potential interaction between Smarca4, NeuroD, and E-cadherin.
In addition to analyzing the three mutants, I have initiated and collaborated on several studies relating to pancreas and heart development. These studies include analyzing the role of Fgf10 in the development of the hepatopancreatic ductal system, the role of Alcam in endodermal and heart development, and testing a model for liver outgrowth.