# Role of Hhip signaling in parallel circuit formation

> **NIH NIH R21** · CHILDREN'S RESEARCH INSTITUTE · 2020 · $209,696

## Abstract

Project Summary/Abstract:
 Loss of vision associated with diseases such as glaucoma, optic nerve hypoplasia, and diabetic
retinopathy is in part caused by the dysfunction and/or premature death of retinal ganglion cells (RGCs), which
transmit all visual information from the eye to the brain. As such, the development of therapies to regenerate
RGCs and re-establish their central connections is a high priority. Visual perception is mediated by integrating
inputs of distinct subtypes of neurons, each of which monitor different aspects of the visual scene, a
phenomenon referred to as parallel processing. The exquisite tuning of individual neurons arises via selective
synapse formation between specific subtypes at each stage of visual processing. Though the presence and
importance of parallel circuits in the visual system are well established, the molecular logic underlying their
assembly remains poorly understood. To bridge this gap in knowledge, we performed a targeted screen to
identify molecules that may regulate parallel circuit connectivity between retinal ganglion cells (RGCs) and
visual neurons in the superior colliculus (SC). In this proposal, we will explore the role of hedgehog interacting
protein (HHIP), which emerged as a top candidate based on its spatially- and temporally-restricted expression
pattern in the SC and previous evidence implicating hedgehog family members in RGC axon guidance. First,
we will test the hypothesis that HHIP is required for the proper targeting of specific subtypes of RGCs in the
SC. Second, we will determine the mechanism by which HHIP guides RGCs by performing in vitro assays on
isolated RGCs. Third, we will test the hypothesis that HHIP is required for the development of specific visual
subcircuits by determining the visual response properties of SC neurons in mice lacking HHIP expression.
Finally, we will elucidate the morphological and functional properties of HHIP+ neurons in the SC by leveraging
a novel transgenic mouse line to label these cells. Taken together, the proposed experiments will elucidate a
novel role for HHIP in neural development and provide critical insight into the poorly understood process of
parallel circuit formation.

## Key facts

- **NIH application ID:** 9843141
- **Project number:** 5R21EY029874-02
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** Jason Triplett
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $209,696
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843141

## Citation

> US National Institutes of Health, RePORTER application 9843141, Role of Hhip signaling in parallel circuit formation (5R21EY029874-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843141. Licensed CC0.

---

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