'Crk'-ing the Code: The role of Crk adaptor proteins in zebrafish eye development

• Main Author: Stergas, Helaina Renee
• Format: Others
• Language: en
• Published: ScholarWorks @ UVM 2018
• Subjects: Cell Biology; Developmental Biology; Neuroscience and Neurobiology
• Online Access: https://scholarworks.uvm.edu/graddis/912; https://scholarworks.uvm.edu/cgi/viewcontent.cgi?article=1912&context=graddis

The migration of neurons from their place of birth to their place of function is an important process during neurodevelopment. Two adaptor proteins, Crk and Crkl, are known to be important factors for neuronal migration. In the neocortex, both molecules play a critical role in the well studied Reelin signaling pathway, guiding newly born neurons to their correct cell layer to create the laminated structure of this tissue. These two adaptor proteins are implicated in human disease of the nervous system. Heterozygous compound deletion of human chromosome 17p13, which includes CRK, occurs in Miller-Dieker syndrome, a severe type of lissencephaly (smooth brain syndrome). Autosomal dominant compound deletion of human chromosome 22q11.2, which includes CRKL, causes DiGeorge Syndrome, a neural crest migratory disease that effects the heart, kidneys, ears, immune system, and face. Danio rerio, or zebrafish, are a great model to study the developing nervous system, and are used in our studies. We characterized expression of crk and crkl at various stages of zebrafish embryo development and determined that both are expressed in the developing eye. We aim to determine if Crk and Crkl have a role in eye development, as the eye and neocortex are very similar in the way they are patterned, and little is known about the signaling mechanisms that guide lamination of the retina. Using mutant knockout lines, we have determined gross retinal phenotypes of Crk deficient, Crkl deficient, and Crk and Crkl compound deficient embryos. Crk and Crkl are both required for proper eye development, as combinations of Crk and Crkl deficiency lead to impaired formation of this tissue. Crk seems to be particularly important for proper eye size, and Crkl is required for proper lamination. This preliminary research is critical to further elucidating the role Crk and Crkl are playing in the retina.