# Investigating Organ Formation and the Emergence of Complexity in the Visual System Using Comparative Developmental Approaches

> **NIH NIH DP5** · HARVARD UNIVERSITY · 2020 · $422,500

## Abstract

Project Summary: Investigating Organ Formation and the Emergence of Complexity in the Visual
System Using Comparative Developmental Approaches
 The visual system has long been at the heart of research into the evolution of complexity in the animal
kingdom. Even Darwin in On the Origin of Species addressed the evolution of the vertebrate eye as a unique
and difficult case in the study of evolution. Despite a long history of research in Drosophila and vertebrate
models, we still understand surprisingly little about how complex organ systems like the visual system are
generated. For example, we have long known that Pax6 and other retinal determination network genes are
essential to eye development in both Drosophila and vertebrates, suggesting a common origin for all visual
organs. However, differences in gene regulatory network connectivity support independent evolution of parts of
this canonical network. This highlights our lack of understanding of how networks change and how they relate
to the complex tissues they underlie. Here we propose to leverage comparative developmental biology to
better understand how gene regulatory networks, protein function, cell fate, and tissue movements evolved to
generate the complexity and diversity within photoreceptive systems found across the animal kingdom. The
power of comparative approaches is that they can reveal non-obvious and conserved mechanisms found
common to organ formation. Recognizing these mechanisms not only deepens our basic understanding of
complex organ development, it can generate new disease candidates and practical new models for human
health. First, we will investigate how complex morphologies of visual organs develop by evaluating cell
behavior and tissue morphogenesis during eye vesicle formation in the cephalopod Doryteuthis pealeii.
Second, we will identify conserved mechanisms generating cell type diversity within the retina, specifically
focused on Notch signaling in neuroepithelial tissues. Lastly, we will evaluate the core retinal determination
gene regulatory network across the animal kingdom using both functional and bioinformatics tools to identify
conserved network connections. This work will be the most in depth analysis to date of the relationship
between gene regulatory networks to cell differentiation and tissue morphogenesis across multiple species.
Our current lack of understanding of this relationship generates a barrier to translate research in model
organisms to effective disease treatment efficiently and this work will shed light on better approaches to these
translational steps.

## Key facts

- **NIH application ID:** 9994778
- **Project number:** 5DP5OD023111-05
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Kristen Marie Koenig
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $422,500
- **Award type:** 5
- **Project period:** 2016-09-21 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994778

## Citation

> US National Institutes of Health, RePORTER application 9994778, Investigating Organ Formation and the Emergence of Complexity in the Visual System Using Comparative Developmental Approaches (5DP5OD023111-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9994778. Licensed CC0.

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