# Mechanisms of signal integration in developmental control of organ size and tissue patterning

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS BOSTON · 2021 · $318,616

## Abstract

PROJECT SUMMARY/ABSTRACT
The proposed work will investigate transcriptional interpretation of signaling through the ERK pathway, which
plays critical roles in animal development and is commonly deregulated in human diseases. We will use
Drosophila as an experimental model that offers unrivaled opportunities for dissecting gene regulation by ERK
signaling at multiple levels of biological organization, from specific ERK substrates to the whole embryo. Aim 1
focuses on Capicua (Cic), a transcriptional repressor that was discovered in Drosophila and has recently
emerged as a key sensor of ERK activation in developmental and pathological contexts. We will identify
functionally significant phosphorylation sites in Cic and investigate their effects on the ERK-dependent control of
Cic protein stability, nuclear localization, and DNA binding. Aim 2 is designed to bridge the gap between genetic
studies, which commonly identify only a handful of ERK substrates, and omics-level studies, which suggest that
ERK functions through large substrate cohorts. We will evaluate these two scenarios using an already working
combination of acute optogenetic perturbations, quantitative phosphoproteomics, and live imaging of functionally
significant transcriptional responses to ERK signaling. Finally, Aim 3 will study transcriptional effects of ERK
signaling, which commonly works by simultaneously activating some cell fates and repressing others. We will
use quantitative optogenetic perturbations and live imaging to test the hypothesis that activating and repressing
effects of ERK signaling require different levels of ERK activation. Our experimental tests of this hypothesis will
address a key issue in developmental ERK signaling and will provide quantitative data needed for predictive
computational modeling. Feasibility of the proposed work is supported by preliminary data that include functional
characterization of Cic phosphosites (Aim 1), a phosphoproteomics approach for the in vivo discovery of ERK
substrates (Aim 2), and an optogenetic approach to data-driven design of predictive computational models (Aim
3).

## Key facts

- **NIH application ID:** 10206726
- **Project number:** 9R01GM141843-06
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS BOSTON
- **Principal Investigator:** Alexey Veraksa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $318,616
- **Award type:** 9
- **Project period:** 2016-08-05 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10206726

## Citation

> US National Institutes of Health, RePORTER application 10206726, Mechanisms of signal integration in developmental control of organ size and tissue patterning (9R01GM141843-06). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10206726. Licensed CC0.

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