# Regulation of apical constriction of bottle cells by the RhoGEF protein Plekhg5 during gastrulation morphogenesis

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $224,692

## Abstract

Apical constriction is a cell shape change that associates with cell ingression, bending of epithelial
sheet, and formation of tubular structures. It is found in many morphogenetic processes, such as
gastrulation, neural tube closure, and sensory organ formation. Failure in apical constriction can
cause human congenital diseases, such as neural tube defects. Despite the importance of apical
constriction in multiple developmental contexts, molecular regulators of apical constriction are not
understood completely. Rho signaling has been implicated previously in apical constriction during
vertebrate neural tube closure and sensory placode invagination. However, general activation of Rho
throughout a cell does not lead to apical constriction, underscoring that polarized stimulation of Rho
within particular subcellular compartment is crucial. Spatial regulation of Rho activities is normally
achieved by Rho regulators GEFs and GAPs. Over 20 members each of RhoGEFs and RhoGAPs
perform diverse cellular functions. The identity of Rho regulators in apical constriction in vertebrates
is not well defined, and the mechanisms via which Rho regulators act to control cell shape changes
are not described in detail. This knowledge gap, combined with the importance of apical constriction
in embryogenesis, demands further investigation about molecular machinery controlling apical
constriction. In our current study, we identified plekhg5 as a RhoGEF expressed in the bottle cells of
the blastopore lip during Xenopus gastrulation and had a function in regulating apical constriction of
the bottle cells. Plekhg5 protein is apically localized and stimulates apical actomyosin assembly to
induce ectopic blastopore lip in a Rho-dependent fashion when ectopically expressed. Knockdown of
plekhg5 blocks apical constriction of bottle cells at the blastopore lip and prevents activin from
inducing blastopore lip in the ectoderm. Plekhg5 is thus an endogenous RhoGEF in bottle cells that
participates in regulation of apical constriction during gastrulation. The activity of plekhg5 provides us
an excellent opportunity to address some of the key issues regarding apical constriction in any tissue
contexts, namely how Rho regulators are recruited to particular subcellular compartment(s) to exert
their function (aim 1); how they modulate dynamic actomyosin organization to coordinate reduction
of apical cell surface and adhesion complex remodeling (aim 2); and how different downstream
effectors are involved in regulating distinct aspects of actomyosin dynamics and cell shape changes
(aim 3). Completion of the proposed studies will offer us deeper insight into molecular control of apical
constriction and provide us a platform to investigate and compare molecular mechanisms governing
apical constriction in diverse tissue contexts. The results may also contribute to our understanding of
human diseases caused by abnormal epithelial morphogenesis due to defects in apical constriction.

## Key facts

- **NIH application ID:** 10385397
- **Project number:** 3R01GM127371-03S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** CHENBEI CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $224,692
- **Award type:** 3
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10385397

## Citation

> US National Institutes of Health, RePORTER application 10385397, Regulation of apical constriction of bottle cells by the RhoGEF protein Plekhg5 during gastrulation morphogenesis (3R01GM127371-03S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10385397. Licensed CC0.

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