Sigma Xi Poster Competition
Effects of Cabin1 loss-of-function in nervous system development
Academic Level at Time of Presentation
Junior
Major
Pre-Veterinary Medicine
Minor
Chemistry
List all Project Mentors & Advisor(s)
Dena Weinberger, PhD
Presentation Format
Poster Presentation
Abstract/Description
Unchecked overproduction of cerebellar cells can lead to medulloblastoma, the most common pediatric brain tumor. Cerebellar granule cells are normally overproduced and pruned into adulthood under the regulation of the transcription factors MADS/myocyte-enhancer-factor 2 (MEF2) and p53. MEF2 and p53 have opposing effects on healthy granule cell populations: MEF2 promotes cell survival and p53 promotes apoptosis. In medulloblastoma, the reverse appears: abnormal p53 activity is associated with tumor proliferation and impaired MEF2 regulation promotes apoptosis of tumor cells, while most other genetic determinants are unknown. Both MEF2 and p53 are regulated by calcineurin-binding-protein 1 (Cabin1). A major obstacle in understanding the roles of Cabin1 in normal cerebellar development and tumorigenesis lies in reconciling that Cabin1 appears to play opposing roles targeting MEF2 and p53 in normal versus diseased cells. Determining where and when Cabin1 is expressed during normal development and understanding its roles therein will provide clarification. Our central hypothesis is that Cabin1 functions in the cerebellum as a negative regulator of MEF2 and p53 to ensure appropriate numbers of granule cells are generated and maintained. We are using behavioral tests to assess the effects on organismal function in Cabin1 loss-of-function mutants. We conclude that loss-of Cabin1 impairs certain behaviors.
Spring Scholars Week 2025
Sigma Xi Poster Competition
Effects of Cabin1 loss-of-function in nervous system development
Unchecked overproduction of cerebellar cells can lead to medulloblastoma, the most common pediatric brain tumor. Cerebellar granule cells are normally overproduced and pruned into adulthood under the regulation of the transcription factors MADS/myocyte-enhancer-factor 2 (MEF2) and p53. MEF2 and p53 have opposing effects on healthy granule cell populations: MEF2 promotes cell survival and p53 promotes apoptosis. In medulloblastoma, the reverse appears: abnormal p53 activity is associated with tumor proliferation and impaired MEF2 regulation promotes apoptosis of tumor cells, while most other genetic determinants are unknown. Both MEF2 and p53 are regulated by calcineurin-binding-protein 1 (Cabin1). A major obstacle in understanding the roles of Cabin1 in normal cerebellar development and tumorigenesis lies in reconciling that Cabin1 appears to play opposing roles targeting MEF2 and p53 in normal versus diseased cells. Determining where and when Cabin1 is expressed during normal development and understanding its roles therein will provide clarification. Our central hypothesis is that Cabin1 functions in the cerebellum as a negative regulator of MEF2 and p53 to ensure appropriate numbers of granule cells are generated and maintained. We are using behavioral tests to assess the effects on organismal function in Cabin1 loss-of-function mutants. We conclude that loss-of Cabin1 impairs certain behaviors.