Honors College Senior Thesis Presentations

Cabin1 Gene Expression in Zebrafish Cerebellum

Presenter Information

Allison TidwellFollow

Academic Level at Time of Presentation

Senior

Major

Biology

Minor

Chemistry

List all Project Mentors & Advisor(s)

Dr. Dena Weinberger

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, both of which are regulated by Calcineurin-binding-protein 1 (Cabin1). MEF2 and p53 have opposing effects on healthy granule cell populations: MEF2 promotes cell survival and p53 promotes apoptosis. In medulloblastoma, the reverse appears: p53 activation is associated with tumor proliferation and MEF2 promotes apoptosis of tumor cells, while most other genetic determinants are unknown. 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 play in normal versus diseased cells. Determining where and when Cabin1 is expressed during normal development and understanding its roles therein will provide clarification. Probes for the genes Cabin1 and marker genes for different cerebellar cell types were designed and synthesized. These probes were then tested for gene expression using in situ hybridization and double in situ hybridization to compare the expression of two genes (slc17a7 and Cabin1) using two probes in the same brain tissue. This would enable us to detect and compare the expression of Cabin1 with the granule cell marker gene slc17a7. We are looking to see if Cabin1 is expressed in those cells or is just in the same area by co-staining for slc17a7. The cell-type specific expression of Cabin1 might prove useful in determining its role in the neuronal development, as the cerebellar granule cells are widely observed through the development stages and into adulthood. Our central hypothesis is that Cabin1 functions in the cerebellum as a negative regulator to ensure appropriate numbers of granule cells are generated and maintained. Establishing roles for Cabin1 in the cerebellum will further our understanding of normal cerebellar development and of the molecular pathways that contribute to brain cancers.

Keywords:

zebrafish

cerebellum

expression

granule

purkinje

development

Cabin1

gene

slc17a7

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Honors College Senior Thesis Presentations

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Cabin1 Gene Expression in Zebrafish Cerebellum

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, both of which are regulated by Calcineurin-binding-protein 1 (Cabin1). MEF2 and p53 have opposing effects on healthy granule cell populations: MEF2 promotes cell survival and p53 promotes apoptosis. In medulloblastoma, the reverse appears: p53 activation is associated with tumor proliferation and MEF2 promotes apoptosis of tumor cells, while most other genetic determinants are unknown. 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 play in normal versus diseased cells. Determining where and when Cabin1 is expressed during normal development and understanding its roles therein will provide clarification. Probes for the genes Cabin1 and marker genes for different cerebellar cell types were designed and synthesized. These probes were then tested for gene expression using in situ hybridization and double in situ hybridization to compare the expression of two genes (slc17a7 and Cabin1) using two probes in the same brain tissue. This would enable us to detect and compare the expression of Cabin1 with the granule cell marker gene slc17a7. We are looking to see if Cabin1 is expressed in those cells or is just in the same area by co-staining for slc17a7. The cell-type specific expression of Cabin1 might prove useful in determining its role in the neuronal development, as the cerebellar granule cells are widely observed through the development stages and into adulthood. Our central hypothesis is that Cabin1 functions in the cerebellum as a negative regulator to ensure appropriate numbers of granule cells are generated and maintained. Establishing roles for Cabin1 in the cerebellum will further our understanding of normal cerebellar development and of the molecular pathways that contribute to brain cancers.

Keywords:

zebrafish

cerebellum

expression

granule

purkinje

development

Cabin1

gene

slc17a7