# Growth factors in the development and physiology of geniculate taste neurons

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $344,985

## Abstract

The lingual sense of taste is initially communicated by taste buds, clusters of sensory cells located in highly
organized taste papillae, to chemosensory neurons whose cell bodies are located in the geniculate and
petrosal ganglia. The chemosensory receptor cells in taste buds continuously turn over and are replaced
throughout life. The molecular mechanisms that direct the developmental innervation of taste buds, and
maintain these constantly renewing functional connections throughout life, are still being elucidated.
Neurotrophic factors are essential for the development and lifelong maintenance of sensory systems. Two
members of the neurotrophin family, BDNF and NT-4, are well established as being critical for the survival of
geniculate chemosensory neurons, and for their innervation of fungiform taste buds. The members of a
second important family of neurotrophic factors, the glial cell line-derived neurotrophic factor (GDNF) family
ligands (GFLs), are expressed in the tongue during the period of chemosensory innervation. The GFLs, which
consist of GDNF, neurturin, artemin and persephin, are potent neurotrophic factors for subpopulations of
somatosensory neurons, spinal motor neurons and autonomic neurons. We recently discovered that the
signal-transducing receptor for the GFLs, Ret, is widely expressed in Phox2B+ chemosensory geniculate
neurons early in development prior to their innervation of the tongue (greater than 70% at E13.5) and then
becomes restricted to a subset (approximately 15%) of Phox2B+ chemosensory neurons in adulthood. This
expression profile suggests that the GFL/Ret pathway may have two distinct developmentally regulated
functions in the differentiation and maintenance of geniculate chemosensory neurons, but their role in the
peripheral taste system is unexplored. Based on preliminary data presented in this proposal, our overarching
hypothesis is that the GFL/Ret receptor complex is critically important for the early cell fate
determination of geniculate chemosensory neurons, as well as for the life-long maintenance and
function of physiologically distinct subpopulations of these neurons. In Specific Aim 1 we will test the
hypothesis that GDNF, NRTN and Ret are critical for the developmental specification of chemosensory
neurons of the geniculate ganglion, as well as their peripheral innervation of fungiform taste buds. In Specific
Aim 2 we will test the hypothesis that the GDNF/Ret receptor complex is necessary for the lifelong
maintenance and physiology of a subset of lingual sensory neurons of the geniculate ganglion. Specific Aim 3
will evaluate whether the peripheral taste system degenerates in mouse models of Alzheimer’s disease. The
rationale for a mechanistic examination of the GFL/Ret pathway in geniculate neurons is that this may aid in
the rational design of therapeutic interventions for diseases, such as Alzheimer’s disease, and injuries of
peripheral neurons.

## Key facts

- **NIH application ID:** 10123642
- **Project number:** 3R01DC015799-05S1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Brian Anthony Pierchala
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,985
- **Award type:** 3
- **Project period:** 2017-06-05 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123642

## Citation

> US National Institutes of Health, RePORTER application 10123642, Growth factors in the development and physiology of geniculate taste neurons (3R01DC015799-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10123642. Licensed CC0.

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