Master of Science
Drysdale, Thomas A.
The pharynx is crucial to the survival of all vertebrates since it facilitates respiration by connecting the nasal and oral cavity to the larynx and digestion by connecting the oral cavity to the esophagus. The developing pharyngeal region displays dorsoventral patterning, and currently there is little information identifying the underlying mechanisms that regulate this patterning. This is in part due to the complexity of the developing pharyngeal region that requires contributions from all three germ layers along with neural crest cells. The expression profiles of Sonic Hedgehog (Shh) and Bone Morphogenetic Protein 4 (Bmp4) adjacent to the developing pharyngeal region are reminiscent of their expression around the developing neural tube where they regulate dorsoventral patterning. By pharmacologically altering these signalling pathways I was able to support the hypothesis that the correct dorsoventral gene expression pattern observed in the developing pharyngeal region is regulated by opposing gradients of Shh and Bmp4.
Summary for Lay Audience
The pharynx is the part of the throat that connects the mouth and nasal cavity to the larynx and esophagus. The purpose of the pharynx is to facilitate respiration by connecting the mouth and nasal cavity to the larynx and allow digestion by connecting the mouth to the esophagus. The developing pharyngeal region can be observed on the lateral side of vertebrate embryos just below the developing head and can be identified by a series of tissue outgrowths called pharyngeal arches. During early development, the pharyngeal region displays patterning of genes along the anteroposterior axis (front to back) and dorsoventral axis (top to bottom). The signaling molecule retinoic acid regulates the patterning of genes along the anteroposterior axis, however, the signaling molecules that regulate the gene pattern along the dorsoventral axis remains unknown. The main aim of this thesis is to uncover those signaling molecules that regulate the dorsoventral patterning of the developing pharyngeal region. The signaling molecules Sonic Hedgehog (Shh) and Bone Morphogenetic Protein 4 (Bmp4) have been shown to regulate the dorsoventral patterning of the neural tube and are expressed later in development on the dorsal and ventral sides of the developing pharyngeal region, respectively. Therefore, I hypothesized that Shh and Bmp4 work in opposing gradients to pattern genes along the dorsoventral axis of the developing pharyngeal region. The hypothesis was tested by chemically inhibiting or activating Shh and Bmp4 signaling, staining the mRNA of genes located within the developing pharyngeal region and assessing the localization of the genes’ expression domains along the dorsoventral axis following treatment of the Xenopus laevis embryos. The results were able to support the hypothesis that the correct gene expression along the dorsoventral axis of the developing pharyngeal region is regulated by opposing gradients of Shh and Bmp4.
Szpak, Alex, "A role for Shh and Bmp4 in regulating the dorsal-ventral patterning of the developing pharyngeal region" (2019). Electronic Thesis and Dissertation Repository. 6673.