# Role of GLI Proteins in Horizontal Basal Cells During Olfactory Epithelium Regeneration

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $37,072

## Abstract

ABSTRACT
The olfactory epithelium (OE) is a specialized neuroepithelium comprised of several cell types, including olfactory
sensory neurons (OSNs), sustentacular cells (SUS), and microvillar cells (MVC), which are replenished by two
presumed stem cell populations: rapidly dividing globose basal cells (GBCs), and relatively quiescent horizontal
basal cells (HBCs). While HBCs and GBCs both contribute to OE regeneration, the signaling pathways that
control this process are not well understood. Recent work indicates that HBCs contain primary cilia, a cellular
organelle that coordinates signals from multiple pathways. Notably, primary cilia are essential for proper
Hedgehog (HH) signal transduction in vertebrates, making the HH pathway an attractive candidate in the control
of HBC function. Further, HH signaling is important in another chemosensory organ, the tongue, where
pharmacologic and genetic HH pathway blockade results in abnormal taste bud maintenance. GLI proteins are
the transcriptional effectors of the HH pathway – GLI1 functions exclusively as a transcriptional activator and is
also a target of HH signaling; GLI2 is the major transcriptional activator of the HH pathway; conversely, GLI3
acts largely as a transcriptional repressor. My preliminary data using lacZ reporter mice suggest that Gli2 is
expressed in all HBCs, while Gli3 is expressed in a subset of HBCs. Additionally, Gli2 expression expands in the
OE following severe injury. To assess possible GLI function in HBCs, I propose to utilize doxycycline-inducible
expression of a constitutively active form of GLI2 to stimulate the HH pathway specifically in HBCs (K5-rtTA;
tetO-GLI2∆N). My preliminary data indicate that HBC-specific activation of GLI2 causes hyperproliferation of
HBCs that are then unable to escape their HBC fate to differentiate and reconstitute the OE after methimazole-
induced injury. Based on these preliminary data, I hypothesize that GLI2 and GLI3 are necessary for OE
regeneration post-injury. I will test this hypothesis by first characterizing the expression of GLI1-3 using cell type
specific markers in both the uninjured and injured adult OE (Aim 1). To access GLI function, I will use the
aforementioned K5-rtTA; tetO-GLI2∆N mice to examine the consequences of constitutive GLI activator function
in both uninjured and injured mice, and conversely use K5-rtTA; tetO-GLI2∆C4 mice to examine the
consequences of constitutive GLI repressor function in uninjured and injured mice (Aim 2). To assess
endogenous GLI function in HBCs, I will delete Gli2 and Gli3 individually and in combination using K5-rtTA; tetO-
Cre, Gli2fl/fl, Gli3fl/fl mice and assess effects on OE maintenance and regeneration following injury. These
experiments will shed light on the signaling pathways that control OE regeneration and further our understanding
of adult neurogenesis.

## Key facts

- **NIH application ID:** 9972744
- **Project number:** 5F31DC018206-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Anna Shirazyan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,072
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972744

## Citation

> US National Institutes of Health, RePORTER application 9972744, Role of GLI Proteins in Horizontal Basal Cells During Olfactory Epithelium Regeneration (5F31DC018206-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9972744. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*