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FRAZZLED/DCC REGULATES SYNAPTOGENESIS AT A DROSOPHILA GIANT SYNAPSE

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Date Issued:
2023
Abstract/Description:
Synaptogenesis is a requirement for cellular communication, but the specific molecular mechanisms underlying synaptogenesis are unclear. Here, we investigate and show the role of the protein Frazzled in synaptogenesis using the transheterozygous Frazzled loss-of-function (LOF) mutant in Drosophila. Leveraging the UAS-GAL4 expression system, we drove expression of various Frazzled/DCC gene constructs in the Giant Fibers (GF) of flies and found changes to synaptogenesis and axon pathfinding. We identified decreases in electrical synaptogenesis and distinct axon pathfinding errors in Frazzled LOF mutants. Strikingly, the expression of Frazzled intracellular domain (ICD) significantly rescues both phenotypes, while full-length Frazzled protein only partially rescues these phenotypes, prompting us to explore the role of different domains within the protein. Deleting the P1 and P2 domains of Frazzled does not rescue axon pathfinding but did partially rescue synaptogenesis while deleting the P3 domain failed to rescue either phenotype. Moreover, when we drive expression Frazzled with a point-mutated P3 domain, silencing its transcriptional activation domain, it fails to rescue both synaptogenesis and axon pathfinding. These results strongly suggest that Frazzled regulates both synaptogenesis and axon pathfinding in the GFs and is necessary for synaptogenesis of the mixed electrochemical GF synapse. Our results provide novel insights into the molecular mechanisms governing neural circuit assembly and highlight Frazzled as a key player in axon guidance and synaptic development.
Title: FRAZZLED/DCC REGULATES SYNAPTOGENESIS AT A DROSOPHILA GIANT SYNAPSE.
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Name(s): Lopez, Juan, author
Murphey, Rodney , Thesis advisor
Florida Atlantic University, Degree grantor
Department of Biological Sciences
Charles E. Schmidt College of Science
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Date Created: 2023
Date Issued: 2023
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 95 p.
Language(s): English
Abstract/Description: Synaptogenesis is a requirement for cellular communication, but the specific molecular mechanisms underlying synaptogenesis are unclear. Here, we investigate and show the role of the protein Frazzled in synaptogenesis using the transheterozygous Frazzled loss-of-function (LOF) mutant in Drosophila. Leveraging the UAS-GAL4 expression system, we drove expression of various Frazzled/DCC gene constructs in the Giant Fibers (GF) of flies and found changes to synaptogenesis and axon pathfinding. We identified decreases in electrical synaptogenesis and distinct axon pathfinding errors in Frazzled LOF mutants. Strikingly, the expression of Frazzled intracellular domain (ICD) significantly rescues both phenotypes, while full-length Frazzled protein only partially rescues these phenotypes, prompting us to explore the role of different domains within the protein. Deleting the P1 and P2 domains of Frazzled does not rescue axon pathfinding but did partially rescue synaptogenesis while deleting the P3 domain failed to rescue either phenotype. Moreover, when we drive expression Frazzled with a point-mutated P3 domain, silencing its transcriptional activation domain, it fails to rescue both synaptogenesis and axon pathfinding. These results strongly suggest that Frazzled regulates both synaptogenesis and axon pathfinding in the GFs and is necessary for synaptogenesis of the mixed electrochemical GF synapse. Our results provide novel insights into the molecular mechanisms governing neural circuit assembly and highlight Frazzled as a key player in axon guidance and synaptic development.
Identifier: FA00014310 (IID)
Degree granted: Master of Science (MS)--Florida Atlantic University, 2023.
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Includes bibliography.
Subject(s): Drosophila
Synapses
Gap Junctions
Receptors, Cell Surface
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00014310
Use and Reproduction: Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Host Institution: FAU