# Supplement to:  Transcription control of retinal neuron specification and maturation

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $73,204

## Abstract

PROJECT SUMMARY/ABSTRACT
Amacrine cells (ACs) are the principle inhibitory neurons of the inner retina, with at least 45 morphologically
distinct subtypes that can be distinguished by the size, shape, and stratification of their dendritic arbors within
the inner plexiform layer (IPL). Most ACs do not have axons, and instead integrate signaling across their
dendritic arbors. This unique arrangement means that form and function are intimately related in ACs,
perhaps more so than in any other neuron type. However, we know virtually nothing about how individual AC
subtypes are specified during development, or how their adopt their stereotyped morphologies. We hypothesize
that selectively expressed transcription factors (TFs) are well poised to direct subtype-specific genetic programs
that specify and direct the morphological maturation of ACs. Within the AC population, the homeodomain TF
Isl1 is only expressed in starburst amacrine cells (SACs) and Gbx2 is only expressed in a previously unidentified
population of medium-field non-GABAeric, non-Glycinergic ACs (MF-nGnGs). Our preliminary results show
that early deletion of Isl1 or Gbx2 from AC precursors results in defects in SAC and MF-nGnG subtype
specification, respectively. Later deletion of Isl1 or Gbx2 in post-migratory SACs or MF-nGnGs alters their
dendritic morphology and stratification patterns. Therefore, Isl1 and Gbx2 appear to be required for the initial
specification and the subsequent morphological maturation of their respective AC subtypes. We will test this in
the following Specific Aims: 1) Determine whether Isl1 and Gbx2 are necessary and sufficient for AC subtype
specification and maturation. We will use conditional loss- and gain-of function approaches to determine
whether Isl1 and Gbx2 are both necessary and sufficient to initiate and maintain terminal differentiation in
SACs and MF-nGnGs, respectively. Furthermore, we will use a combination of genomic approaches (RNASeq,
ATACseq) to identify the Isl1 and Gbx2 gene regulator networks in the respective AC subtypes. 2) Define how
Isl1 and Gbx2 regulate SAC and MF-nGnG morphology and functional connectivity. We will first identify how
the loss of Isl1 in SACs and Gbx2 in MF-nGnGs affects the development of their stereotyped dendritic
morphology and stratification patterns. Then we will test candidate effector genes and pathways for their
involvement in the establishment of dendritic arbors. Finally, we will determine how the loss of Isl1 and Gbx2
affects the functional connectivity of SACs and MF-nGnGs in visual circuits. Together, these experiments are
expected to reveal how selectively expressed transcription factors specify AC subtypes and drive terminal
differentiation programs that endow ACs with their unique morphological properties. We expect that these
findings will reveal principles that are broadly applicable across the developing nervous system.

## Key facts

- **NIH application ID:** 10429697
- **Project number:** 3R01EY032057-01S1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Kevin Wright
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $73,204
- **Award type:** 3
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429697

## Citation

> US National Institutes of Health, RePORTER application 10429697, Supplement to:  Transcription control of retinal neuron specification and maturation (3R01EY032057-01S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10429697. Licensed CC0.

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