# Understanding trigeminal ganglion development through the lens of Familial Dysautonomia

> **NIH NIH R03** · UNIV OF MARYLAND, COLLEGE PARK · 2022 · $77,250

## Abstract

PROJECT SUMMARY
Cranial neural crest cells (NCCs) and placode cells (PCs) differentiate to form diverse cell types, including
sensory neurons, cartilage and bone, and skin pigment cells. Abnormalities that occur during NCC and PC
development are thus directly responsible for many human diseases, including Familial Dysautonomia (FD), a
sensory and autonomic nerve disorder characterized, in part, by cranial trigeminal ganglion (TG) dysfunction.
Both NCCs and PCs must coalesce together to assemble the TG, which relays somatosensory information from
the head to the brain. The dual cellular origin of the TG evokes questions regarding how two distinct cell
populations interact to form a single tissue, which constitutes a significant gap in knowledge. In this proposal,
we will investigate molecular mechanisms underlying TG development through pioneering studies in both mouse
and chick model systems. Our preliminary data demonstrated progressive morphological deficits in the TG and
its nerves in a mouse model of FD in which the causative gene, Elongator Complex Protein 1 (Elp1), is deleted
in NCCs and their derivatives (Elp1 CKO). Moreover, specific TG neuron subpopulations that sense pain and
temperature (nociceptors) are depleted in Elp1 CKO embryos, providing a cellular basis for the phenotypes
observed in FD. Altogether, these findings reveal a critical role for Elp1 in TG development; however, the
molecular mechanisms by which Elp1 orchestrates the proper establishment of the TG remain largely unknown.
Since Elp1 possesses diverse, context-dependent functions, unbiased approaches are required to examine the
role of Elp1 exclusively in the TG. To this end, we will use mass spectrometry (MS) at distinct developmental
stages to address our working model that Elp1 mediates downstream signaling required for proper formation of
the TG and its nerves. The Specific Aims of this application are to: 1) determine the effects of NCC Elp1 loss on
the TG proteome and 2) define cell-type specific Elp1-interacting proteins in the TG. In Aim 1, we will delineate
the TG proteome in Elp1 CKO vs. littermate controls, identifying candidates whose expression is affected by
Elp1 loss. Candidate function will be evaluated in the mouse and chick, with the latter possible due to
conservation of Elp1 expression, providing the ability to rapidly perform functional experiments. In Aim 2, we will
use affinity-based MS to uncover Elp1 binding partners in the TG specific to PCs (revealed in the Elp1 CKO) and
NCC derivatives (identified in controls after comparison to Elp1 CKO), with candidate evaluation proceeding as
in Aim 1. The proposed research is innovative because it combines the power of two complementary
developmental models (mouse and chick) with a multidisciplinary approach involving embryology, biochemistry,
proteomics, and novel microscopy and perturbation assays. These results will significantly advance our
knowledge of the molecular mechanisms underscoring intercellu...

## Key facts

- **NIH application ID:** 10432307
- **Project number:** 1R03HD108480-01
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** LISA A TANEYHILL
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $77,250
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10432307

## Citation

> US National Institutes of Health, RePORTER application 10432307, Understanding trigeminal ganglion development through the lens of Familial Dysautonomia (1R03HD108480-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10432307. Licensed CC0.

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