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Development of Specific Neuron-Glia Attachments

Award Number: R01NS112343
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2019
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Development of Specific Neuron-Glia Attachments - Abstract During development, cells adhere to specific partners in precise arrangements to build well-ordered structures. Nowhere is this more impressive than in the brain, which has the most diverse cell types with the most elaborate morphologies and most highly specific connectivity of any organ. While extensive work has been done to identify mechanisms of partner selection among neurons, far less is known about neuron-glia pairing. Glia extend membranous processes that intimately wrap specific synapses, affecting synapse growth and pruning, and modulating synapse strength during learning. Defects in glia-neuron interactions are associated with a host of neurodevelopmental disorders. Thus, understanding how specific neuron-glia attachments are determined will shed light on a key aspect of brain wiring, and will reveal general principles by which cells select specific adhesion partners during development. This project uses a single defined neuron-glia attachment as a model to identify the developmental and genetic mechanisms that underlie neuron-glia pairing. It focuses on a single C. elegans sensory neuron, called URX, that forms membranous attachments to a specific glial partner, the lateral ILso glial cell. Highly cell-type-specific drivers allow this single, defined neuron-glia contact to be visualized or genetically manipulated in live intact animals. Preliminary data show that this specific neuron-glia attachment arises in embryos by a multi-step developmental process. First, the URX dendrite anchors to a 'guidepost' glial cell during embryo elongation, positioning the dendrite ending at the nose tip. Then, a sensory cilium grows out of the dendrite tip to form the elaborate attachment to the ILso glial partner. This project will investigate: Aim 1. How does the dendrite anchor to the guidepost cell? Preliminary data suggest that epithelial adherens junctions are modified to create the anchoring site. Aim 2. How does the sensory cilium mediate neuron-glia adhesion? Preliminary genetic screens have identified several mutants that disrupt cilia adhesion, including one that affects a proteoglycan with homology to a protein that mediates glia-synapse interactions in mammalian brain. Aim 3. What is the function of this highly specific neuron-glia attachment? Preliminary work indicates that the attachment undergoes experience-dependent remodeling, suggesting a mechanism by which glia could tune the sensitivity of the neuron by altering the physical structure of its receptive ending.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $522,803 )
2026	2026	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	12/19/2025	NON-COMPETING CONTINUATION	$522,803
														Subtotal = $522,803

Issue Date FY: 2025 ( Subtotal = $600,141 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	12/24/2024	NON-COMPETING CONTINUATION	$540,128
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	7/22/2025	NON-COMPETING CONTINUATION	$60,013
2025	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	3/14/2025	COMPETING CONTINUATION	$1,909
2025	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	3/14/2025	NON-COMPETING CONTINUATION	-$1,909
														Subtotal = $600,141

Issue Date FY: 2024 ( Subtotal = $527,665 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	12/19/2023	COMPETING CONTINUATION	$527,665
2024	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/11/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $527,665

Issue Date FY: 2022 ( Subtotal = $387,188 )
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	6/14/2022	NON-COMPETING CONTINUATION	$387,188
														Subtotal = $387,188

Issue Date FY: 2021 ( Subtotal = $387,188 )
2021	2021	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/8/2021	NON-COMPETING CONTINUATION	$387,188
														Subtotal = $387,188

Issue Date FY: 2020 ( Subtotal = $387,188 )
2020	2020	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/8/2020	NON-COMPETING CONTINUATION	$387,188
														Subtotal = $387,188

Issue Date FY: 2019 ( Subtotal = $387,188 )
2019	2019	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/15/2019	NEW	$387,188
														Subtotal = $387,188

Grand Total All Awards = $3,199,361

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Development of Specific Neuron-Glia Attachments

Award Number: R01NS112343

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2019

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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