| NSF Org: |
IOS Division Of Integrative Organismal Systems |
| Recipient: |
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| Initial Amendment Date: | July 26, 2018 |
| Latest Amendment Date: | May 19, 2023 |
| Award Number: | 1755340 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Laura N. Borodinsky
lborodin@nsf.gov (703)292-4958 IOS Division Of Integrative Organismal Systems BIO Directorate for Biological Sciences |
| Start Date: | August 1, 2018 |
| End Date: | August 31, 2024 (Estimated) |
| Total Intended Award Amount: | $137,000.00 |
| Total Awarded Amount to Date: | $137,000.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
21 GRAHAM AVE CORTLAND NY US 13045-2452 (607)753-2511 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
21 Graham Avenue Cortland NY US 13045-2542 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | Organization |
| Primary Program Source: |
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| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
This project examines how appropriately-functioning neuronal circuits are made as embryos develop and grow. The work focuses on circuits in the spinal cord of zebrafish embryos, which develop early in life and are simpler and more experimentally-tractable than neural circuits in the brain. The goal is to identify key regulatory genes that instruct cells to grow into one particular population of nerve cells (interneurons) with specific functions in controlling precise body movements. The outcomes of this project will be widely applicable, because these types of nerve cell exist in all vertebrates (including humans). The genes identified in this study and the ways that they influence nerve cell and circuit development are likely to be similar in many different species. This project will significantly increase understanding of how genes instruct cells to develop with particular characteristics, and the roles that specific genes play in the construction of neuronal circuitry. The principal investigators will incorporate this research into their university teaching and presentations made to the general public. This research will contribute to the diversification of the scientific workforce through the active participation of both women and under-represented minorities. The principal investigators will also perform outreach to local city high schools and develop teaching modules for both 9th/10th grade and advanced placement high school Biology students. The aim of these activities is to significantly impact the lives of traditionally under-served high school students and enthuse under represented minority high school students about science and research.
An essential first step in understanding how neuronal networks are generated is determining how distinct interneurons (INs) are specified with particular functional properties. One key property that helps to define INs is which neurotransmitter they use to communicate with other cells. Neurotransmitters can be excitatory or inhibitory and INs utilizing inappropriate neurotransmitters form malfunctioning circuits. Therefore, determining how IN neurotransmitter properties are specified is crucial for understanding both IN and circuit development. Relatively little is known about how excitatory spinal IN properties are specified. This proposal will characterize a gene regulatory network (GRN) that specifies spinal IN excitatory properties, using zebrafish as a model system. The investigators have identified genes that encode for 11 different DNA-binding proteins as candidate members of a GRN that specifies V0v IN excitatory (glutamatergic) properties. V0v INs reside in the middle of the spinal cord and have crucial roles in locomotor circuitry. The research team has already shown that four of these genes, evx1/2 and lmx1ba/b are required for correct excitatory fates of V0v INs. In addition, in evx1/2 double mutants V0v INs lose expression of both lmx1ba/b and the other 7 genes, suggesting that all 9 of these genes may act downstream of Evx1/2 in specifying V0v glutamatergic properties. The specific objectives of this proposal are to test if any of these 7 other genes are required for correct V0v neurotransmitter properties and determine the epistatic relationships among all of these Evx1/2-regulated genes. Single and compound zebrafish mutants will be used to answer these questions.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
As a single-cell embryo develops into a multicellular organism, some cells become neurons and produce neurotransmitters—chemical messengers that enable neurons to communicate within neural circuits. These circuits are networks of interconnected neurons that process information, control responses, and regulate behavior. Neurotransmitters determine whether a neuron excites or inhibits its synaptic partner, which is essential for proper circuit function. Disruptions in this process can impair neural circuits and affect the organism’s behavior.
The choice of which neurotransmitter a neuron synthesizes is regulated by transcriptional regulator genes. These genes produce proteins that control the activation and/or inhibition of other genes, guiding neurons to adopt specific functions. In this project, we studied the gene regulatory network (GRN) that directs the excitatory fate of V0v neurons, a specific population of interneurons in the vertebrate spinal cord. Our work aimed to identify previously unknown transcriptional regulator genes involved in regulating glutamate neurotransmitter production in these neurons using zebrafish as a model system. In this project we developed new experimental approaches and reagents to show that there are two molecularly distinct zebrafish V0v neurons by 48hrs of embryonic development consistent with prior findings in mice, highlighting conserved nature of neuronal development in vertebrates. We also identified 36 transcriptional regulator genes expressed in V0v neurons were able to identify genetic interactions between some of these transcriptional regulators. Our data suggests that some of these genes are needed for V0v interneurons to develop correctly, while others must be turned off to prevent these cells from adopting different roles. This balance appears to be crucial for ensuring that V0v interneurons maintain their identity and contribute to neural circuits as excitatory cells. We have also generated additional reagents that would be used to investigate which transcriptional regulators are required for the development of V0v neurons as excitatory glutamatergic neurons.
This project has resulted in two scientific publications and three poster presentations at international conferences featuring the work of SUNY Cortland undergraduate students. It has provided direct research internship experiences for four SUNY Cortland undergraduate students, including three women and one woman from an underrepresented minority group. Through this collaborative grant, these students from a primarily undergraduate institution (SUNY Cortland) had the opportunity to conduct summer research at a R01 institution (Syracuse University). All four students presented their research at regional conferences, and three were co-authors on posters presented at international conferences. Additionally, this grant facilitated research opportunities for five more SUNY Cortland students. The findings of this project have been instrumental in teaching SUNY Cortland’s first Neurobiology (BIO 450) course and in supporting outreach activities at nearby Homer High School and the Rosamond Gifford Zoo in Syracuse.
Last Modified: 12/13/2024
Modified by: Santanu Banerjee
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