Characterizing the Role of Crk in Central Nervous System Development in Drosophila

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  • May 5, 2020
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  • Bonner, Alison
    • Affiliation: College of Arts and Sciences, Department of Biology
Abstract
  • While determining the roles that different functional domains of Abelson tyrosine kinase (Abl), a key developmental regulator and oncogene, during normal development, our lab was surprised to find that a short, conserved motif (PXXP) in the linker region was more important for Abl’s morphogenic roles than both kinase activity and F-actin binding. This finding led us to hypothesize that Crk binding to Abl’s PXXP motif is critical for mediating Abl’s developmental functions. Crk family proteins, including Crk and Crk-like (Crk-L), are a well-conserved family of small adaptor proteins that play a role in cell adhesion, migration, and other biological processes during normal development. Crk also plays a role in various cancers, including invasive bladder cancer, and Crk-L is a key mediator of oncogenic forms of Abelson tyrosine kinase (Abl) in Leukemia. Based on Abl’s well-defined roles in central nervous system (CNS) patterning, we hypothesized that Crk might be required for proper CNS patterning. To test this hypothesis, I used RNAi to deplete Crk both maternally and zygotically in embryos and asked what effect, if any, this had on embryonic viability and CNS patterning. Using this approach, I found that Crk is required for embryonic viability and that loss of Crk results in CNS patterning defects. To better understand the mechanism(s) by which Crk may alter CNS patterning, I am looking at the Robo/Slit repulsive axon guidance cues in the Crk knock down embryos to determine if the CNS patterning defects observed are the result of loss of Crk affecting this pathway. I found that localization of these proteins remains largely normal and their function appears unaltered, indicating that this pathway is intact and does not require Crk. Preliminary analysis suggests that zygotic loss of crk also results in partially penetrant CNS patterning defects, mimicking what we see using an RNAi approach. We are continuing to characterize morphogenic defects associated with loss of Crk to determine its Abl-dependent and – independent roles. This work will help provide better insight into Crk’s roles during normal development and disease states.
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  • In Copyright
Advisor
  • Peifer, Mark
Degree
  • Bachelor of Science
Academic concentration
  • Biology
Honors level
  • Honors
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2018
Language
  • English

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