Impact of nmda receptors on neural crest development
Active Project Grant Awarded Last action
- Award ID
- F30HD122415
- Recipient
-
The Research Foundation For The State University Of New York UEI M746VC6XMNH9 Part of The Research Foundation For The State University Of New York
- Awarding agency
-
National Institute of Child Health and Human Development
National Institutes of Health, Department of Health and Human Services
- Obligated
- $42,647
Award facts
- Assistance listing
- 93.865 Child Health and Human Development Extramural Research
- Completion date 0% complete
- Place of performance
- Stony Brook, NY 11794, USA
Award details come from USAspending.gov.
Description
- Abstract
- Autism spectrum disorder, attention-deficit hyperactivity disorder, and intellectual disability fall under the umbrella of neurodevelopmental disorders, which affect approximately 15% of children and adolescents worldwide. Neurodevelopmental disorders are mainly linked to aberrations in the development and function of the central nervous system (CNS). Neurodevelopmental disorders are common in individuals with disease- associated variants in the grin family of genes that encode subunits of nmda receptors (NMDARS). NMDARS are glutamate-gated ION channels fundamental to signaling in the CNS. While these individuals exhibit CNS dysfunctions, many individuals also experience symptoms in non-CNS tissues that can cause major daily challenges, such as issues with sensory, enteric, and autonomic nervous systems. Interestingly, these non-CNS impairments often involve tissues derived from the neural crest, a unique population of cells that migrates extensively during development and forms numerous body structures. Despite this connection, the role of the neural crest in the pathogenesis of neurodevelopmental disorders remains poorly understood. Preliminary data demonstrate that zebrafish lacking nmdar signaling have abnormalities in tissues derived from the neural crest. Preliminary data also indicate that NMDARS may modulate neural crest cell proliferation through cell cycle regulation and WNT/Β-catenin signaling. Since neural crest cells are non-synaptic during development, these data suggest NMDARS play a non-traditional role in regulating neural crest behavior. Importantly, NMDARS are composed of multiple subunits, including GLUN1, which is obligatory, and GLUN2A- D, which varies by tissue and across time. The GLUN2 specificity in neural crest is completely unknown yet critical to define in terms of understanding mechanisms and defining treatment options. My central hypothesis is that specific GLUN2 subunits drive the regulation of neural crest cell proliferation and WNT signaling activity. To test this hypothesis, I will use zebrafish to model the loss-of-function of specific GLUN2 subunits and assess the impact on the cell cycle of neural crest cells using a dynamic CDK activity biosensor (aim 1) and WNT signaling activity in neural crest cells using various transgenic zebrafish reporters of WNT signaling activity (aim 2). This work will clarify how non-CNS symptoms arise in neurodevelopmental disorders and can guide the development of targeted treatments to ameliorate the day-to-day challenges faced by these individuals. Completion of the proposed study aims under the mentorship of an interdisciplinary team of experts in development and imaging (DR. Benjamin martin) and NMDARS (DR. Lonnie wollmuth) will provide the applicant with an excellent foundation for becoming a well-rounded physician-scientist.
Quick answers
Who received award F30HD122415?
F30HD122415 was awarded to The Research Foundation For The State University Of New York by National Institute of Child Health and Human Development (National Institutes of Health) on February 1, 2027.
How much is award F30HD122415 worth?
$42,647 has been obligated on F30HD122415.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award