# An integrative cellular blueprint of vertebrate tissue development

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $750,000

## Abstract

Project Summary / Abstract
Every animal begins as a single cell. How this cell ultimately gives rise to a vertebrate animal possessing millions to trillions of cells, each specialized to perform specific functions in a variety of organ systems, remains a
fundamental question in biology. Until now, in toto capture of the collective cellular behaviors that generate the
vertebrate body plan has not been possible. We have assembled a team with complementary expertise in
developmental genetics, tissue patterning, imaging, and quantitative biology that will synergize to take lineage
analysis in vertebrates to an entirely new level. We will utilize the unique strengths of the zebrafish, combined
with recent advances in genetic fate mapping techniques, high-resolution, whole-animal 4D microscopy, and
computational methodologies to derive its complete lineage map. Our proposed approaches are precise, enabling prospective and retrospective lineage analyses, and they are visual, enabling direct identification and
quantification of cell behaviors. We have developed indelible marking systems to laser-target single cells in
the embryo and permanently activate reporter gene expression. Clonal analysis beyond the embryo will involve inducible Cre recombinases and single/multicolor Cre-releasable reporter transgenes. Our toolset will
allow any cell of interest and its progeny to be followed for life. By deriving a library of thousands of labeled
animals, we will create unprecedented access to the biography of each organ. To complement our cellular
tagging approaches, we will develop imaging platforms to elucidate the entire progeny sets of labeled clones
and their tissue distribution. We will also develop novel computational methods to track clones across development and to generate a digitized map that recapitulates the cellular dynamics that underlie the adult body
plan. Clonal data sets will be utilized to develop probabilistic models to infer how proliferation and differentiation dynamics give rise to observed lineage restriction. Collectively, this massive technological achievement
will yield templates of organ morphogenesis that we will make facile for any user to access, visualize, and manipulate. These body plan reconstructions can be employed as a baseline for interpreting cell lineage decisions in response to tissue damage, genetic manipulation, or malignancy.

## Key facts

- **NIH application ID:** 10001627
- **Project number:** 5R01OD026219-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Zhirong Bao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $750,000
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001627

## Citation

> US National Institutes of Health, RePORTER application 10001627, An integrative cellular blueprint of vertebrate tissue development (5R01OD026219-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001627. Licensed CC0.

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