# Genetic Dissection of Signaling and Cilia

> **NIH NIH R35** · EMORY UNIVERSITY · 2023 · $463,601

## Abstract

Project Summary/Abstract
 Cilia sparked phenomenal interest as scientists recognized them as a fundamental cellular organelle
required for signaling. Untangling the specific mechanisms that regulate Sonic hedgehog (Shh) signaling within
the cilium is difficult since so many mutants that disrupt ciliogenesis also affect Hh signaling. We have long
focused on a small ciliary GTPase, ARL13B, that we hypothesize integrates the regulation of ciliogenesis and
Hh signaling through distinct effectors and their downstream pathways. As a GTPase, single basepair
mutations within the GTPase domain of ARL13B are predicted to disrupt individual effector pathways. ARL13B
is highly enriched in cilia. By engineering mouse expressing only an ARL13B variant that does not localize to
cilia, we genetically uncoupled the role of ARL13B in ciliogenesis from its role in signaling. We focus on
mammalian neural development and through forward genetic screens identified mouse mutants in several
proteins related to ARL13B. Additionally, other proteins in the ARL family of GTPases are implicated in cilia
and signaling through what appear to be ARL13B related mechanisms. In the next five years, we propose
using mouse mutants to define the regulatory relationships among these players in vivo and in specific cell
types. These experiments will unravel ARL13B function in ciliogenesis, traffic of proteins to/within cilia, and
Shh signal transduction at unprecedented resolution. Thus, our proposal will generate a molecular genetic
toolkit from which the field will be poised to distinguish the regulation of cilia from that of Hh signaling. This is
important to our fundamental understanding of cilia, ciliogenesis and cilia structure, as well as our basic
comprehension of the Hh pathway.

## Key facts

- **NIH application ID:** 10556629
- **Project number:** 1R35GM148416-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** TAMARA J. CASPARY
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $463,601
- **Award type:** 1
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10556629

## Citation

> US National Institutes of Health, RePORTER application 10556629, Genetic Dissection of Signaling and Cilia (1R35GM148416-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10556629. Licensed CC0.

---

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