Embryonic Expression and Roles of Neuronal Connexin 35 in Zebrafish Spinal Cord

Summary

Principal Investigator: Tara Martin
Abstract: DESCRIPTION (provided by applicant): A goal of neurodevelopmental biology is to identify mechanisms by which normal paterning of the nervous system occurs to ultimately apply this knowledge to understanding neurodevelopmental disorders. Activity-dependent processes have been recognized as important mechanisms for early neurodevelopment and electrical synapses have been suggested to play an integral role in the establishment and refinement of neuronal networks. Electrical synapses are formed with gap junction communications between neuronal cells that allow for the direct transfer of current. The proteins responsible for most gap junction formations, connexins, have been implicated in a number of neurodevelopmental processes. However, increasing evidence indicates connexins play more than a pore-forming role, but may also participate in other intracellular and extracellular interactions that can have profound effects on development. The goal of the current study is to determine the role neuronal specific connexins play in neurodevelopment by exploring the many possible mechanisms by which these protein complexes may mediate developmental control. This study takes advantage of the Danio rerio (zebrafish) model to determine whether the neuronal specific connexin 35 (Cx35) plays a fundamental role in the development of the spinal cord. The two specific aims will test the hypotheses that (1) proper development of the zebrafish spinal cord requires developmentally regulated expression of Cx35 and (2) the mechanism by which Cx35 mediates neurodevelopment may be executed by pore function and/or intracellular interactions. The experimental approach utilizes a number of tools available in zebrafish, such as the availability of many transgenic lines, easy genetic manipulation, live- imaging, and pharmacological approaches. Aim 1 will use in situ hybridization (ISH) and immunohistochemistry (IHC) to determine the cx35 mRNA expression profile and morpholino knockdown to determine if Cx35 is required for proper development of spinal cord cells in order to elucidate the cellular networks that require Cx35 for proper development. Aim 2 wil use a pharmacological approach to uncouple gap junctions and the production of transgenic lines that express mutant forms of Cx35 to determine whether Cx35 developmental control is mediated by pore-dependent and/or pore-independent molecular processes. The role of connexin proteins in early development has not been fuly explored. Much of the current knowledge regarding connexins in the nervous system is on their role in fine-tuning already established networks. Investigating the role of connexins in early development may help deepen our understanding of the importance of these proteins in establishing complex neuronal networks and determining cellular development.
Funding Period: 2011-07-01 - 2014-06-30
more information: NIH RePORT

Research Grants

  1. Synaptic Function: Effects of the Nerve Injury, Repair, and Altered Activity
    Timothy C Cope; Fiscal Year: 2013
  2. Identification of genes that regulate electrical synapse formation in vivo
    Cecilia B Moens; Fiscal Year: 2013
  3. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013
  4. Alzheimer's Disease Research Center
    Douglas R Galasko; Fiscal Year: 2013
  5. Expanding Excellence in Developmental Biology in Oklahoma
    Linda F Thompson; Fiscal Year: 2013
  6. Molecular and Cellular Therapies for Muscular Dystrophy
    Stanley C Froehner; Fiscal Year: 2013
  7. Center for Neuroplasticity at the University of Puerto Rico
    Steven N Treistman; Fiscal Year: 2013
  8. SULT4A1 Function in Zebrafish Development
    Charles N Falany; Fiscal Year: 2013
  9. Strategies for Improved Shock Wave Lithotripsy
    JAMES ALEXANDER MCATEER; Fiscal Year: 2013

Detail Information

Research Grants30

  1. Synaptic Function: Effects of the Nerve Injury, Repair, and Altered Activity
    Timothy C Cope; Fiscal Year: 2013
    ..The Resume and Summary of Discussion above summarizes the final outcome of the group discussion. OVERALL PROGRAM EVALUATION ..
  2. Identification of genes that regulate electrical synapse formation in vivo
    Cecilia B Moens; Fiscal Year: 2013
    ..A fundamental understanding of how synapses are built is essential for improved detection of neurological disease and for guiding the development of therapies. ..
  3. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013
    ....
  4. Alzheimer's Disease Research Center
    Douglas R Galasko; Fiscal Year: 2013
    ..It will provide an environment and core resources to enhance research, foster professional and community training, and coordinate interdisciplinary research. ..
  5. Expanding Excellence in Developmental Biology in Oklahoma
    Linda F Thompson; Fiscal Year: 2013
    ..abstract_text> ..
  6. Molecular and Cellular Therapies for Muscular Dystrophy
    Stanley C Froehner; Fiscal Year: 2013
    ..The mechanism of NPC1 phenotype amelioration and its applicability to LGMDs will be studied. Two core facilities will serve the participating laboratories. ..
  7. Center for Neuroplasticity at the University of Puerto Rico
    Steven N Treistman; Fiscal Year: 2013
    ..This UPR COBRE Center should define pathways and benchmarks for basic and translational research across the UPR system for the next decades. ..
  8. SULT4A1 Function in Zebrafish Development
    Charles N Falany; Fiscal Year: 2013
    ..Aim 3 To investigate the activity and substrate selectivity of SULT4A1 using the zebrafish embryo/larval developmental system. ..
  9. Strategies for Improved Shock Wave Lithotripsy
    JAMES ALEXANDER MCATEER; Fiscal Year: 2013
    ..and the session can be ended * Determine the mechanism by which cavitation within a vessel causes hemorrhage * Develop numerical models to understand the role of cavitation and non-cavitational mechanisms in causing tissue damage ..