# Micropattern differentiation and morphogenesis of the human ectoderm

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2024 · $353,565

## Abstract

Project Summary/Abstract
How accurate cell fate specification occurs in the context of dynamic tissue-scale
rearrangements is one of the most exciting questions in developmental biology. In
this proposal we aim at deciphering the interplay between fate acquisition,
patterning and morphogenesis of the ectodermal germ layer in the context of
human neurulation. We have recently developed a robust protocol which allows
for the generation of extremely reproducible human neuruloids: self-organized
human Embryonic Stem Cell (hESC) assemblies that recapitulate the organization
of the ectodermal compartment at neurulation stages by organizing neural, neural
crest, placodes and epidermis populations within the same colony on adhesive
micropatterns. This self-organization is extremely reproducible and can be
quantified with sub-cellular resolution and in real time over hundreds of colonies.
Armed with this novel technology, we propose three specific aims. The first is to
unravel the mechanism of cell-cell signaling driving self-organization. The second
is to integrate signaling with fate acquisition and morphogenesis through live
reporter imaging and time dependent single cell RNAseq. Finally, the third aim
focuses on the full characterization of the origin and sub-populations of ectodermal
derivatives and their in vivo validation by performing side by side comparisons with
stage-matched marmoset fetal samples and grafting experiments in chick
embryos. The generation of large numbers of homogenous human neuruloids,
where self-organization of ectodermal fate can be followed dynamically for a period
of one week, with sub-cellular resolution, not only solves the inherent
heterogeneity observed in cerebral organoids, but provides us a unique
opportunity to study these events in models of human embryos. This will have a
high impact in both basic research as well as clinical application, a prospect
already on the horizon.
!

## Key facts

- **NIH application ID:** 10885095
- **Project number:** 5R01HD102757-05
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** ALI H BRIVANLOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $353,565
- **Award type:** 5
- **Project period:** 2020-08-24 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885095

## Citation

> US National Institutes of Health, RePORTER application 10885095, Micropattern differentiation and morphogenesis of the human ectoderm (5R01HD102757-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10885095. Licensed CC0.

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