# Genetic Regulation of Developmental and Regenerative Growth

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $612,169

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall goal of our research is to understand the mechanisms that regulate growth: at the level of the
individual cell, at the level of organs and at an organismal level. In order to study the regulation of growth, we
have studied the imaginal discs of Drosophila, the larval precursors of adult structures such as the wing.
Until recently, an important limitation to our work was that we had few tools to study the cellular heterogeneity
that is a key feature of growth regulation in vivo. Single-cell transcriptomics allows us to characterize small
subsets of cells that have a major impact on growth regulation. By combining this approach with experimental
genetics, we can now study a key aspects of growth regulation that involves heterotypic interactions between
small subsets of cells.
We aim to obtain a better understanding of the genetic regulation of regenerative growth. We have identified a
gene regulatory network that is entirely dispensable for normal development but is essential for regenerative
growth. Additional genes identified from our single-cell studies point to genes that are specifically expressed in
different portions of the regeneration blastema and which likely regulate different aspects of regeneration
including proliferation, cell shape and cell-fate plasticity. We will characterize the function of these genes. We
have also found that damage and regeneration of one portion of the disc can impact the development of the
remainder of the disc and also distant organs. Another goal is to elucidate the mechanistic basis of these long-
range phenomena.
We will examine the role of ion channels in regulating Hedgehog signaling and the growth and patterning of the
of the wing disc. We will determine why cells with a more depolarized membrane potential survive
preferentially in the anterior compartment of the wing disc. We will also study the properties of the
mechanosensitive channel Piezo in growth regulation.
Finally, by combining our single cell atlas of the wing disc with a genetic screen, we have identified many
genes encoding poorly-characterized cell-surface proteins and ligand-receptor pairs that likely function during
development to regulate cell survival, cell proliferation and planar cell polarity. We will study these genes.

## Key facts

- **NIH application ID:** 10604383
- **Project number:** 5R35GM122490-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Iswar K. Hariharan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $612,169
- **Award type:** 5
- **Project period:** 2017-04-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10604383

## Citation

> US National Institutes of Health, RePORTER application 10604383, Genetic Regulation of Developmental and Regenerative Growth (5R35GM122490-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10604383. Licensed CC0.

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