# DIVERSITY SUPPLEMENT TO DEVELOPMENTAL ORIGINS AND HOMEOSTATIC MECHANISMS UNDERLYING ADULT PHENOTYPES

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2022 · $53,793

## Abstract

PROJECT SUMMARY
Parent award. Mechanisms underlying the origin and maintenance of adult form, and naturally occurring varia-
tion in adult form, remain poorly understood. This research program seeks to elucidate how gene activities are
translated through cellular behaviors into speciﬁc morphological outcomes at adult stages. Such information
will contribute to understanding patterning and morphogenetic mechanisms essential for postembryonic devel-
opment, with relevance to human genetic disease, birth defects, aging and regenerative medicine. For these
efforts, the work uses pigmentation of zebraﬁsh, its close relatives in the genus Danio, and more distantly re-
lated teleost ﬁshes. Pigment cells in these animals and other vertebrates arise from embryonic neural crest
cells that also contribute to a wide variety of other tissues and organs, including most of the peripheral nervous
system and craniofacial skeleton. Defects in neural crest derived lineages generally, and pigment cells speciﬁ-
cally, are associated with numerous hereditary pathologies as well as cancers, including melanoma. During
normal development, pigment cells that arise either directly from neural crest cells or indirectly through
postembryonic stem cell intermediates organize into highly stereotyped, largely two dimensional patterns in the
transparent skin. Cell behaviors during pattern formation are readily observed as phenotypes develop, and ge-
netic mechanisms are accessible through mutational analyses and other approaches, both in striped zebraﬁsh
and in other species having very different adult patterns. The work described here builds on prior effort in this
program, and takes an unusually integrative approach to understand pattern and pattern variation, combining
manipulative experiments, genetic analysis, high resolution imaging, cutting edge genomics, comparative biol-
ogy and behavioral assays. Goals in the coming years are to elucidate: (i) mechanisms by which pigment cell
progenitors are speciﬁed for different pigment cell types during development, and how diversiﬁcation of cell
types has been achieved evolutionarily; (ii) genetic and cellular mechanisms underlying self-organizing interac-
tions among pigment cells that are essential for pattern formation, and how these interactions and permissive
factors have changed to generate alternative pattern states among species; (iii) the roles of positional informa-
tion in the tissue environment in setting the location of discrete pattern elements that are essential for estab-
lishing pattern, and how such information contributes to qualitatively different types of pattern across species.
These efforts will provide novel insights into pattern development and cell type diversiﬁcation over both devel-
opmental and evolutionary time. General principles uncovered will likely be applicable to a wide range of traits
that depend to varying degrees cell type diversiﬁcation, self-organizing cellular interactions, and positional i...

## Key facts

- **NIH application ID:** 10622666
- **Project number:** 3R35GM122471-07S1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** DAVID M PARICHY
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $53,793
- **Award type:** 3
- **Project period:** 2017-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10622666

## Citation

> US National Institutes of Health, RePORTER application 10622666, DIVERSITY SUPPLEMENT TO DEVELOPMENTAL ORIGINS AND HOMEOSTATIC MECHANISMS UNDERLYING ADULT PHENOTYPES (3R35GM122471-07S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10622666. Licensed CC0.

---

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