Date on Master's Thesis/Doctoral Dissertation

12-2025

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Biochemistry and Molecular Biology

Degree Program

Biochemistry and Molecular Biology, PhD

Committee Chair

Lovely, Charles B.

Committee Member

Smith, Melissa

Committee Member

Woo, Stephanie

Committee Member

Samuelson, David

Committee Member

Fernandes, Yohaan

Author's Keywords

FASD; zebrafish; planar cell polarity; endoderm; jaw development; craniofacial

Abstract

Fetal Alcohol Spectrum Disorders (FASD) describes a large range of developmental defects due to prenatal alcohol exposure. It is characterized by neural and facial defects, including jaw hypoplasia. Many factors contribute to the susceptibility of ethanol-induced facial defects, including genetics, yet the genes involved, and the cell events they regulate, are poorly understood. Zebrafish have a large number of tools for genetic manipulation available, share 70% of genes with humans, are fertilized externally and are translucent during embryogenesis, making them great models to study FASD. Previous studies show that two members of the Planar Cell Polarity (PCP) pathway, zebrafish vangl2 and gpc4, are ethanol sensitive when treated with 1% (v/v) ethanol from 6-24 hours post fertilization (hpf) and when exposed to ethanol exhibit multiple defects including those to the jaw. Proper formation of the anterior pharyngeal endoderm (APE), which occurs between 10-24 hpf, is necessary for jaw development. Previous work showed that the PCP pathway is involved in convergence and extension (C&E) of the endoderm and gastrulation from 6-10 hpf. However, it is unknown if the PCP pathway plays a role in APE morphogenesis after gastrulation, and if ethanol disrupts APE morphogenesis. I hypothesize that loss in vangl2 and gpc4 lead to ethanol-induced jaw defects when treated from 10-24 hpf after gastrulation, and that this is exacerbated in double mutants. Using morphometric analyses, my results reveal that both vangl2 and gpc4 mutant embryos exhibit jaw hypoplasia when treated with ethanol from 10-24 hpf. Ethanol-induced jaw defects are exacerbated in double mutants, as well as mutant/heterozygous combinations. I go on to show that vangl2 and gpc4 are expressed in the endoderm from 10-24 hpf, and their mutants experience APE defects. Overall, this suggests that ethanol-sensitive vangl2 and gpc4 genes play a role in APE morphogenesis and subsequently jaw development.

Download

Share

COinS