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Molecular and anatomical atlases from progenitors to adult neurons in the mouse spinal cord

Award Number: R01MH134799
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Molecular and anatomical atlases from progenitors to adult neurons in the mouse spinal cord - The developing spinal cord has long been a classic model for understanding neurodevelopmental mechanisms yet linking developmental cell types to their adult counterparts has proved elusive. Developmental transcription factors are required for the differentiation and specification of cell types during embryogenesis and are expressed in discrete domains in the developing spinal cord. Yet in the adult, expression of these developmental transcription factors is lost making it difficult to connect embryonic progenitor domains to their adult cell types and function. We will address this gap in knowledge by tracking developmental lineages over time using genetic lineage tracing of molecularly-defined progenitor domains and assaying the changes in transcription, epigenome, and anatomical distribution. Comprehensive understanding of the developmental lineages will reveal true structural and functional complexity of spinal cord circuits that are not reflected in single- cell transcriptomics of adult tissue. We will focus on the developing dorsal progenitor domains that give rise to adult cell types of the dorsal to intermediate spinal cord. The dorsal spinal cord is the primary area for integration of somatosensory stimuli from the periphery and consists of the senses of nociception (pain), thermosensation (temperature), mechanosensation (touch), pruriception (itch), and proprioception (limb and body position). The goal of this proposal is to generate three types of mouse atlases. In Aim 1, we will generate a molecular signature developmental atlas that catalogs the transcriptional and epigenomic changes of dorsal progenitor domain lineages using the 10x Genomics Multiome platform. We have identified five CRE-recombinase mouse lines that together will isolate progenitor domains of the developing spinal cord. We will use these lines to assay the molecular signatures of these lineages at three major time points across the lifetime of the animal and along the rostral-caudal axis. In Aim 2, we will generate an anatomical phenotype developmental atlas to understand the distribution of the molecular signatures using standard histological techniques and a multiplexed spatial transcriptomics platform, MERSCOPE. In Aim 3, we will create a molecular lineage 3-dimensional atlas of all five CRE-lineages at adult stages using the TissueCyte platform. Altogether, these three atlases will provide an invaluable resource for the spinal cord and somatosensory neuroscience community. Comprehensive cell profiling of the dorsal spinal cord will catalog spinal cell types in native states that can be compared to injured or diseased states. It will also serve as a reference for the cell type profiling of the spinal cord in other species. Furthermore, by adding on a layer of developmental lineage, we will answer long standing questions about the development of the spinal cord. Understanding this developmental relationship will provide insight into whether a particular adult cell type is constrained by its developmental lineage, how discrete progenitor domains generate the diversity of cell types in the adult spinal cord and lay the necessary foundation for cell-type regeneration and engineering efforts for spinal cord tissue.


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 = $1,110,530 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	3	11/28/2025	NON-COMPETING CONTINUATION	$1,110,530
														Subtotal = $1,110,530

Issue Date FY: 2025 ( Subtotal = $1,129,792 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	2	11/22/2024	NON-COMPETING CONTINUATION	$1,129,792
														Subtotal = $1,129,792

Issue Date FY: 2024 ( Subtotal = $1,303,492 )
2024	2024	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	1	3/1/2024	NEW	$1,303,492
														Subtotal = $1,303,492

Grand Total All Awards = $3,543,814

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Molecular and anatomical atlases from progenitors to adult neurons in the mouse spinal cord

Award Number: R01MH134799

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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