Tuesday, April 23, 2024 4/23/2024

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

Award Number: R01GM127371
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	4	3/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	4	4/14/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $321,692 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	4	2/25/2022	NON-COMPETING CONTINUATION	$289,520
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	001	4	7/27/2022	NON-COMPETING CONTINUATION	$32,172
														Subtotal = $321,692

Issue Date FY: 2021 ( Subtotal = $546,384 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	3	2/25/2021	NON-COMPETING CONTINUATION	$321,692
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	001	3	9/14/2021	SUPPLEMENT FOR EXPANSION	$224,692
														Subtotal = $546,384

Issue Date FY: 2020 ( Subtotal = $321,841 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	2	2/24/2020	NON-COMPETING CONTINUATION	$321,841
														Subtotal = $321,841

Issue Date FY: 2019 ( Subtotal = $333,668 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	1	2/26/2019	NEW	$333,668
														Subtotal = $333,668

Grand Total All Awards = $1,523,585

Top

All Categories

About

Search

Reports

Data Submission

Award Information

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

Award Number: R01GM127371

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer