# Peripheral activity-dependent and molecular mechanisms that control somatosensory system development

> **NIH NIH K99** · HARVARD MEDICAL SCHOOL · 2022 · $99,972

## Abstract

Project Summary
The sense of touch is essential for life, and alterations in tactile sensory inputs early in development may
cause long-term consequences on health and behavior. In mammals, non-painful touch is detected by low-
threshold mechanoreceptors (LTMRs), peripheral sensory neurons that innervate the skin and relay tactile
information to the central nervous system (CNS) by forming synapses in the spinal cord and brainstem. How
mechanical or molecular cues from the periphery influence the development of LTMRs and their downstream
circuits remains poorly understood. In particular, the developmental mechanisms underlying the central
circuitry engaged by LTMRs and the brain's somatotopically organized and disproportionate responses to
touch of different body regions remain unclear. The proposed work will use mouse genetic, anatomical,
electrophysiological, and molecular approaches to investigate the role of developmental neural activity and
skin type-specific signals that shape the structural and functional development of somatosensory neurons and
their downstream circuits. In Aim 1, Dr. Santiago will use conditional ion channel mutants to define the role of
spontaneous and evoked activity during the maturation of mechanosensory end organ structures in the
periphery. Aim 2 will move into the CNS and assess the requirement for peripherally-mediated activity during
LTMR central targeting and synapse formation, as well as during somatotopic map formation. Dr. Santiago will
use a new mouse transgenic line to transiently silence somatosensory neurons during defined developmental
periods, before restoring touch sensation and measuring the responses of central neurons to tactile stimuli. In
Aim 3, Dr. Santiago will use target-specific RNA sequencing of somatosensory neurons, surgical
manipulations, and genetic approaches to identify target-dependent molecular mechanisms by which cues in
the skin control LTMR identity and connectivity. These proposed experiments will be paired with a scientific
training plan in electrophysiology and the analysis of bioinformatic data, as well as a career development plan
preparing Dr. Santiago to become an independent researcher. Technical and conceptual guidance on
designing and performing electrophysiological and RNA sequencing experiments will be provided by the team
of consultants that the candidate has assembled that includes Drs. Bruce Bean, Chinfei Chen, Lisa Goodrich,
and Michael Greenberg. The candidate's mentor, Dr. David Ginty, will supervise the mentored phase of the
award through regular meetings and ensure that Dr. Santiago's training fully prepares her to transition to an
independent position. Together, the proposed research and training plan will enable Dr. Santiago to make
important discoveries concerning the role of peripherally-mediated activity and molecular cues in
somatosensory system development and prepare her to lead an independent research group addressing
outstanding questions in neural dev...

## Key facts

- **NIH application ID:** 10349098
- **Project number:** 1K99NS124993-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Celine Santiago
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $99,972
- **Award type:** 1
- **Project period:** 2021-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10349098

## Citation

> US National Institutes of Health, RePORTER application 10349098, Peripheral activity-dependent and molecular mechanisms that control somatosensory system development (1K99NS124993-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10349098. Licensed CC0.

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