# CRISPR based screen for small GTPase regulators of morphogenesis in Xenopus

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $225,625

## Abstract

Abstract
Many birth defects arise from flaws in the cell behaviors that drive normal tissue organization, including the
prevalent cases of neural tube defects, and craniofacial defects. There has been considerable progress in
understanding the mechanics of cell behavior; in contrast, the upstream control, at the level of cytoskeletal
regulatory proteins, and the transcriptional control of expression of the regulators has been documented in fewer
cases. Nonetheless, we can point to several examples where a specific morphogenetic event is ultimately
regulated by the expression of genes that encode regulators of small GTPases, particularly Rho. Here we
hypothesize that we will gain insights into many embryonic contexts of morphogenesis by screening directly for
regulators of small GTPases that are essential for subsets of the early morphogenetic events of gastrulation and
neurulation. Rather than conduct open-ended screens, we focus on GTPase Regulators, where we have argued
that there is a precedent for their general importance in morphogenesis. There are about 150 Rho GAPs and
GEFs listed in the community database, Xenbase, with descriptions of their temporal expression, and
sometimes, their transcript localization. We will prioritize genes that are zygotically expressed to avoid regulators
of general cellular processes, and then knock out targets using G0 (aka F0) Crispr, which is sufficient to identify
phenotypes. Using high-throughput imaging we will screen for phenotypes associated with gastrulation and
neurulation defects. Hits will then be further characterized to determine if they are locally or globally expressed.
This project will ultimately generate the molecular tools to manipulate and analyze the force generation and
intercellular interactions that determine how cells move in the embryo. As with the insights into neural tube
defects that have come from understanding neurulation movements in frogs, we will establish principles to
examine other morphogenetic events and failures that lead to birth defects.

## Key facts

- **NIH application ID:** 10354182
- **Project number:** 1R21HD107363-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Richard M Harland
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,625
- **Award type:** 1
- **Project period:** 2021-09-17 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354182

## Citation

> US National Institutes of Health, RePORTER application 10354182, CRISPR based screen for small GTPase regulators of morphogenesis in Xenopus (1R21HD107363-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10354182. Licensed CC0.

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