RNA Topoisomerase in Neural Circuit Development: A Zebrafish Story
Primary Faculty Mentor’s Name
Vinoth Sittaramane
Proposal Track
Student
Session Format
Paper Presentation
Abstract
Many enzymes play key roles in living systems and their neurodevelopment over time. Mutations in the protein sequence of these enzymes could alter its function in system growth and expansion. One class of enzymes in particular, known as topoisomerases, helps to maintain DNA structure during replication and transcription. A recent addition to this class is an RNA topoisomerase found in vertebrates. Observations in a Northern Finnish human population have identified mutations in this topoisomerase (TOP3B) that lead to neurodevelopmental disorder characteristics of Schizophrenia, Fragile X Syndrome, and Autism-Spectrum Disorder (ASD). Previous studies in fruit flies and mouse neuronal cell cultures have identified roles in neural development and synapse formation for Top3B. However, invivo role of top3B during development and adulthood in a vertebrate model system remains unclear. Our current research focuses on in vivo studies in zebrafish (Danio rerio) neurological development with this topoisomerase. Preliminary studies with RNA in situ hybridization have identified top3B expression in the forebrain, notochord, and retinotectal pathways. Anti-sense morpholino-based knockdowns of top3B reveal defasciculation of spinal motor axons, an expanded notochord, and failure of retinal lamination along the retinotectal pathway. Expression patterns in early zebrafish embryo development have strong implications of where top3B mutations will take effect; knockdowns indicate developmental defects in regions where top3B is expressed. Together, our data implicates top3B roles in olfactory axon development, neuromuscular junction formation, and retinal layer formation. Further quantification of spinal motor neurons affected by the absence of top3B is important to indicate numerical significance in synapse formation. Observation of increased synaptic boutons is expected, in hopes of finding a correlation between zebrafish and human synaptic disorders throughout early development. Success in these experiments will encourage quicker matriculation in future drug screening and therapies against disorders affecting brain synapses, helping to record motor activity in an efficient manner.
Keywords
Biology, Neurobiology, Zebrafish, Brain, Autism
Location
Room 1909
Presentation Year
2014
Start Date
11-15-2014 8:30 AM
End Date
11-15-2014 9:30 AM
Publication Type and Release Option
Presentation (Open Access)
Recommended Citation
Williams, Kori S., "RNA Topoisomerase in Neural Circuit Development: A Zebrafish Story" (2014). Georgia Undergraduate Research Conference (2014-2015). 5.
https://digitalcommons.georgiasouthern.edu/gurc/2014/2014/5
RNA Topoisomerase in Neural Circuit Development: A Zebrafish Story
Room 1909
Many enzymes play key roles in living systems and their neurodevelopment over time. Mutations in the protein sequence of these enzymes could alter its function in system growth and expansion. One class of enzymes in particular, known as topoisomerases, helps to maintain DNA structure during replication and transcription. A recent addition to this class is an RNA topoisomerase found in vertebrates. Observations in a Northern Finnish human population have identified mutations in this topoisomerase (TOP3B) that lead to neurodevelopmental disorder characteristics of Schizophrenia, Fragile X Syndrome, and Autism-Spectrum Disorder (ASD). Previous studies in fruit flies and mouse neuronal cell cultures have identified roles in neural development and synapse formation for Top3B. However, invivo role of top3B during development and adulthood in a vertebrate model system remains unclear. Our current research focuses on in vivo studies in zebrafish (Danio rerio) neurological development with this topoisomerase. Preliminary studies with RNA in situ hybridization have identified top3B expression in the forebrain, notochord, and retinotectal pathways. Anti-sense morpholino-based knockdowns of top3B reveal defasciculation of spinal motor axons, an expanded notochord, and failure of retinal lamination along the retinotectal pathway. Expression patterns in early zebrafish embryo development have strong implications of where top3B mutations will take effect; knockdowns indicate developmental defects in regions where top3B is expressed. Together, our data implicates top3B roles in olfactory axon development, neuromuscular junction formation, and retinal layer formation. Further quantification of spinal motor neurons affected by the absence of top3B is important to indicate numerical significance in synapse formation. Observation of increased synaptic boutons is expected, in hopes of finding a correlation between zebrafish and human synaptic disorders throughout early development. Success in these experiments will encourage quicker matriculation in future drug screening and therapies against disorders affecting brain synapses, helping to record motor activity in an efficient manner.
