# Tracing developmental signaling histories with imaging-based molecular recording

> **NIH GM R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2026 · $433,125

## Abstract

Project Summary
Signals that cells receive over time from a small set of pathways (e.g., BMP, Wnt, and TGFβ) shape their fate
and phenotype during development, regeneration, and disease. Despite their central importance, signaling
histories of individual cells are often inaccessible to direct observation, hindering quantitative analysis and
obscuring their connection to eventual cell fate. This challenge is particularly pronounced in mammalian
systems, where limited optical access and the constraints of size and timescale often render live imaging
impractical. To address this issue, we have developed an approach to reconstruct the history of signaling
activity in single cells based on endpoint fluorescence images. This is achieved by regulating CRISPR base
editors to generate mutations in engineered target sites at rates proportional to the signal of interest. These
mutations create a heritable record of signaling activity in the genome, which can be read out at a later time,
together with the gene expression profile of the cells. Using this approach, we demonstrated that cells retain a
memory of their past response level to BMP signaling for up to 18 days, providing a mechanism for long-term
interactions between signals that can facilitate coordination of developmental processes over time.
In this proposal, we will expand the scope and utility of our signal recording approach by extending its dynamic
range to capture the broad spectrum of in vivo signal intensities and enabling simultaneous recording of the
sequence and timing of two signaling pathways. We will also engineer mouse embryonic stem cells to record
three key developmental pathways: BMP, Wnt, and Nodal. This will allow us to generate stem cell-derived
embryo models and chimeric embryos to link cell fate and spatial organization at the onset of organogenesis
with signaling activity at different time windows earlier in development. Additionally, we will investigate
mechanisms that enable long-term changes

## Key facts

- **NIH application ID:** 11271618
- **Project number:** 1R35GM162272-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Amjad  Askary
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $433,125
- **Award type:** 1
- **Project period:** 2026-04-01T00:00:00 → 2031-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11271618

## Citation

> US National Institutes of Health, RePORTER application 11271618, Tracing developmental signaling histories with imaging-based molecular recording (1R35GM162272-01). Retrieved via AI Analytics 2026-07-08 from https://api.ai-analytics.org/grant/nih/11271618. Licensed CC0.

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