# Integration of spatiotemporal signaling for pattern formation and scaling

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $449,499

## Abstract

Abstract
Tissues and organs display characteristic patterns established during embryonic development. Segmentation
of somites, precursors of vertebrae, is a unique example in which spatial patterns are established sequentially
and periodically. The prevailing clock and wavefront (CW) model states that the period of segmentation is set
by the oscillatory expression of the Hes/her gene family (the segmentation clock). Disrupting these oscillations
causes vertebral defects. The CW model further states that the positions of segment boundaries are
determined by a critical readout of a signaling gradient (i.e. the wavefront) in the middle of the presomitic
mesoderm (PSM). Depending on the stage, three to five compartments are predetermined to segment. We
recently developed a novel 3D explant culture of zebrafish PSM and discovered that the FGF-mediated double
phosphorylated ERK (ppERK) gradient is the wavefront. We also showed that in three popular vertebrate
models (fish, chick and mice), anterior somite lengths are uniform but posterior somite lengths scale with the
length of PSM. This scaling phenomenon contributes to the generation of species-specific segment numbers.
Several important questions remain unsolved: 1) What mechanism controls segment length scaling, 2) How
the clock and ppERK gradient are integrated to govern segmentation, and 3) How cells decode the
spatiotemporal information, provided by the clock and ppERK gradient, to commit to segmentation in mid-PSM.
To address these fundamental questions, we will perturb the clock, gradient or cell polarity machinery in a
spatiotemporally-controlled manner, visualize their readouts at the single-cell level, and combine quantitative
data analysis with mathematical modeling to test alternative mechanistic hypotheses: Aim 1: Discover the
mechanism governing pattern size scaling. Aim 2: Discover the mechanism integrating the segmentation clock
with the wavefront. Aim 3: Discover the mechanism decoding spatiotemporal information of the clock and
wavefront. Hes/Her oscillations and FGF/ERK activity control pattern formation in various tissues during
development. Disruption of their activities also result in specific cancer types. Our work might inspire future
investigations on their roles during development of other tissues and how their dysregulations result in birth
defects and cancer. Therefore, this application has strong relevance to the mission of the National Institute of
Health.

## Key facts

- **NIH application ID:** 11085830
- **Project number:** 7R01HD103623-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ertugrul M Ozbudak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $449,499
- **Award type:** 7
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11085830

## Citation

> US National Institutes of Health, RePORTER application 11085830, Integration of spatiotemporal signaling for pattern formation and scaling (7R01HD103623-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11085830. Licensed CC0.

---

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