# Development and evolution of self-organizing pigmentation patterns

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2022 · $352,919

## Abstract

Project Summary
The emergence of complex tissue patterns from seemingly uniform, undifferentiated cells during
development is an essential feature of all multicellular organisms. One of the most prominent theoretical
mechanisms often invoked to explain biological pattern formation is the reaction-diffusion (RD) model, which
postulates that local activation of pattern differentiation factors combined with long-range inhibition of the
activity of those factors can produce dynamic, self-organizing spatial patterns. Numerous empirical and
simulation studies have suggested that the RD mechanism underlies a wide range of pattern formation
processes. However, we still know very little about the actual genes encoding the hypothetical activation
and inhibition factors in most empirical systems, even less about the biophysical properties of these factors
where candidate genes have been identified, and virtually nothing about how modulation of the properties of
these activators and inhibitors affects pattern evolution in nature. The overall objective of this project is to
address these fundamental questions by elucidating the detailed genetic and developmental mechanisms of
pigment pattern formation and evolution in the wildflower genus Mimulus (monkeyflowers), a system
amenable to rigorous genetic analysis, developmental interrogation, and phenotypic perturbation. The work
proposed here will build on our prior efforts that identiﬁed a pair of MYB proteins underlying the formation of
dispersed anthocyanin pigment spots in Mimulus flowers. This MYB pair forms a local autocatalytic
feedback loop and a long-range inhibitory feedback loop, fulfilling the tenets of a classical activator-inhibitor
RD model. Our goals in the coming years are to: (i) experimentally determine the biophysical properties of
the activator-inhibitor pair, including their diffusion coefficients, degradation (clearance) rates, and relative
activation and inhibition constants; (ii) characterize the genetic and developmental bases of pattern
evolution from dispersed spots to longitudinal stripes between closely related species; and (iii) identify the
key cis-regulatory elements that constitute the activator-inhibitor interacting network and test the function of
this two-component, activator-inhibitor module in other tissue types and heterologous systems. Towards
these ends we will use a suite of approaches, including fluorescence imaging, genetic mapping, transgenic
manipulation, and mathematical modeling. Together our efforts will provide an in-depth view of how the RD
mechanism generates self-organizing spatial patterns and modulates pattern evolution in a real biological
system, lending empirical support to the mathematically elegant but somewhat controversial RD model.

## Key facts

- **NIH application ID:** 10317040
- **Project number:** 5R01GM140092-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Yaowu Yuan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $352,919
- **Award type:** 5
- **Project period:** 2020-12-15 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317040

## Citation

> US National Institutes of Health, RePORTER application 10317040, Development and evolution of self-organizing pigmentation patterns (5R01GM140092-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10317040. Licensed CC0.

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