Identifying the molecular underpinnings of regenerative heterogeneity in dorsal root ganglia (DRG)

Active Project Grant Awarded Last action

Award ID
F31NS149592
Recipient
Awarding agency
Obligated
$43,565

Award facts

Assistance listing
93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
Completion date 0% complete
Place of performance
La Jolla, CA 92093, USA

Award details come from USAspending.gov.

Description

Abstract
Spinal cord injury (SCI) causes lasting disability due to the limited ability of CNS neurons to regenerate axons. Even with genetic interventions, only a subset of neurons regrow their axons after injury, revealing significant heterogeneity in their regeneration responses. A recent study from our lab used patch-SEQ, a technique that collects single cells from acute tissue slices under visual guidance, to identify two novel regeneration-related gene hubs in corticospinal (CST) motor neurons. Using these data, our lab developed a regeneration classifier to predict regenerative potential from gene expression profiles of single neurons. However, the basis of this classifier is currently limited to CST neurons and one experimental context. To address this limitation and investigate regeneration in a vastly different neuronal type, this proposal studies dorsal column nuclei (DCN)-projecting dorsal root ganglion (DRG) sensory neurons, some of which can regenerate their central axons following a peripheral conditioning lesion. The proposed work tests the hypothesis that transcriptional heterogeneity among DCN-projecting drgs drives their variable regenerative responses and that including this data will expand the applicability of the regeneration classifier. To test this hypothesis, the proposed study will use an intersectional viral tracing strategy to label DRG neurons that do and DON't regenerate their central axons following a peripheral conditioning lesion. Aim 1 employs a candidate approach to determine what types of DRG neurons regenerate. To do this, planned experiments will characterize whether different DRG subtypes have different regenerative abilities using genetic mouse lines. Aim 2 employs an unbiased approach using patch-SEQ to identify gene hubs that underlie differential outcomes of regenerating and non-regenerating drgs. The single-cell transcriptomic data generated from aim 2 will be analyzed to identify new regeneration regulators and will be incorporated into the previously developed regeneration classifier to enhance its applicability for predicting regenerative potential across diverse neuronal types and injury conditions.

Quick answers

Who received award F31NS149592?

F31NS149592 was awarded to University Of California, San Diego by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on December 1, 2026.

How much is award F31NS149592 worth?

$43,565 has been obligated on F31NS149592.

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