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Development and evolution of self-organizing pigmentation patterns

Award Number: R01GM140092
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Development and evolution of self-organizing pigmentation patterns - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $352,919 )
2024	2024	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Biomedical Research and Research Training	001	4	6/20/2024	NON-COMPETING CONTINUATION	$35,292
2024	2024	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Biomedical Research and Research Training	000	4	12/13/2023	NON-COMPETING CONTINUATION	$317,627
														Subtotal = $352,919

Issue Date FY: 2023 ( Subtotal = $352,919 )
2023	2023	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Biomedical Research and Research Training	001	3	3/31/2023	NON-COMPETING CONTINUATION	$35,292
2023	2023	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Biomedical Research and Research Training	000	3	11/21/2022	NON-COMPETING CONTINUATION	$317,627
														Subtotal = $352,919

Issue Date FY: 2022 ( Subtotal = $352,919 )
2022	2022	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Biomedical Research and Research Training	000	2	11/19/2021	NON-COMPETING CONTINUATION	$317,627
2022	2022	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Biomedical Research and Research Training	001	2	8/3/2022	NON-COMPETING CONTINUATION	$35,292
														Subtotal = $352,919

Issue Date FY: 2021 ( Subtotal = $352,919 )
2021	2021	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Biomedical Research and Research Training	000	1	12/10/2020	NEW	$352,919
														Subtotal = $352,919

Grand Total All Awards = $1,411,676

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Development and evolution of self-organizing pigmentation patterns

Award Number: R01GM140092

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/15/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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