Presentation Title

Crk adaptor proteins are necessary for the development of the zebrafish retina

Project Collaborators

Alicia Ebert (Advisor), Bryan Ballif (Collaborating PI)

Abstract

The development of the nervous system requires intricate cell communication to tightly regulate important processes such as cellular migration, proliferation, and survival, to create the functional adult tissue. The CRK adaptor protein family (CRK and CRK-like, or CRKL) is known to play an integral role in cell signaling needed for these developmental processes by clustering upstream and downstream signaling molecules to propagate cell communication. Both molecules function in Reelin signaling to regulate neuronal migration responsible for patterning laminated tissues such as the cortex, cerebellum, and hippocampus. Due to the role of CRK and CRKL in neuronal migration, we aimed to determine if these proteins are important for development of another laminated central nervous system tissue, the retina. Using zebrafish as a model system, we generated stable knockout lines of both genes using CRISPR/Cas9. Embryos lacking both Crk and Crkl have gross phenotypic abnormalities including heart edema, brain edema, and statistically smaller eye size when compared to wildtype sibling control embryos. Transverse sections through the forebrain of these embryos reveals lamination defects within the retina, demonstrating that Crk and Crkl play a crucial role in patterning this tissue. Interestingly, the lamination phenotype is variable, suggesting possible compensation between Crk adaptors, as well as between other adaptor proteins that may play similar functions within the retina. Currently, we are focusing on the genetic and functional compensation mechanisms at play in our mutant lines that lead to this variability.

Primary Faculty Mentor Name

Alicia Ebert

Status

Graduate

Student College

Graduate College

Program/Major

Biology

Primary Research Category

Biological Sciences

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Crk adaptor proteins are necessary for the development of the zebrafish retina

The development of the nervous system requires intricate cell communication to tightly regulate important processes such as cellular migration, proliferation, and survival, to create the functional adult tissue. The CRK adaptor protein family (CRK and CRK-like, or CRKL) is known to play an integral role in cell signaling needed for these developmental processes by clustering upstream and downstream signaling molecules to propagate cell communication. Both molecules function in Reelin signaling to regulate neuronal migration responsible for patterning laminated tissues such as the cortex, cerebellum, and hippocampus. Due to the role of CRK and CRKL in neuronal migration, we aimed to determine if these proteins are important for development of another laminated central nervous system tissue, the retina. Using zebrafish as a model system, we generated stable knockout lines of both genes using CRISPR/Cas9. Embryos lacking both Crk and Crkl have gross phenotypic abnormalities including heart edema, brain edema, and statistically smaller eye size when compared to wildtype sibling control embryos. Transverse sections through the forebrain of these embryos reveals lamination defects within the retina, demonstrating that Crk and Crkl play a crucial role in patterning this tissue. Interestingly, the lamination phenotype is variable, suggesting possible compensation between Crk adaptors, as well as between other adaptor proteins that may play similar functions within the retina. Currently, we are focusing on the genetic and functional compensation mechanisms at play in our mutant lines that lead to this variability.