Tuesday, July 1, 2025 7/1/2025

Molecular Mechanisms of Regeneration Termination

Award Number: R01HD108059
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

Molecular Mechanisms of Regeneration Termination - Project Summary The molecular mechanisms by which stem cell proliferation is precisely controlled during the course of regeneration are poorly understood. Namely, how a damaged tissue senses when to terminate the regeneration process, inactivates stem cell mitotic activity, and organizes ECM integrity remain fundamental unanswered questions. Uncontrolled proliferation of stem cells in regenerative tissues can result in tumor formation. The Drosophila midgut intestinal stem cell (ISC) has recently emerged as an attractive model system to study tissue homeostasis and regeneration. This is due to striking similarities in genetic control and cellular composition between the Drosophila and mammalian digestive systems, and powerful genetic tools available in this model. Importantly, Drosophila ISC proliferation is promoted in response to tissue damage to stimulate tissue repair. Using this model system, a number of studies have been conducted to reveal the pathways that activate ISC proliferation. Despite a wealth of knowledge on the activation of proliferative capacity of stem cells, it is largely unknown how the tissue properly down-regulates stem cell proliferation at the end of regeneration and how this process is linked to epithelial remodeling. We recently established the Drosophila ISCs as an excellent model to study the molecular basis for regeneration termination. Using RNA-seq, we identified sets of genes and pathways that are up/down-regulated at different phases of regeneration. Among these, we found that dMOV10, a component of the microRNA (miRNA) gene silencing complex, is required for the proper termination of the regeneration process. Further analyses identified direct target mRNAs of dMOV10-containing miRISC, including baboon (the Type I receptor of activin signaling) and two major non- integrin ECM receptors, Syndecan (a transmembrane heparan sulfate proteoglycan) and Dystroglycan (an integral membrane component of the dystrophin-glycoprotein complex). In addition to the identification of dMOV10 as a termination stage-specific gene, this same RNA-seq analysis showed that key components for septate junctions, and actin regulators are specifically upregulated during regeneration and return to normal level at a late stage. In this proposal, we will define these key molecules in stem cell inactivation and ECM remodeling at the termination stage of Drosophila midgut regeneration through the following Specific Aims. Aim 1. Determine the role of septate junction components in midgut regeneration. Aim 2. Define the role of Sdc and Dg in ECM remodeling. Aim 3. Define the global landscape of the miRNA-mediated network.


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: 2025 ( Subtotal = $329,365 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Child Health and Human Development Extramural Research	001	4	4/14/2025	NON-COMPETING CONTINUATION	$32,936
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Child Health and Human Development Extramural Research	000	4	2/12/2025	NON-COMPETING CONTINUATION	$296,429
														Subtotal = $329,365

Issue Date FY: 2024 ( Subtotal = $326,072 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Child Health and Human Development Extramural Research	001	3	5/1/2024	NON-COMPETING CONTINUATION	$29,643
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Child Health and Human Development Extramural Research	000	3	12/19/2023	NON-COMPETING CONTINUATION	$296,429
														Subtotal = $326,072

Issue Date FY: 2023 ( Subtotal = $329,365 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Child Health and Human Development Extramural Research	000	2	12/24/2022	NON-COMPETING CONTINUATION	$296,429
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Child Health and Human Development Extramural Research	001	2	2/10/2023	NON-COMPETING CONTINUATION	$32,936
														Subtotal = $329,365

Issue Date FY: 2022 ( Subtotal = $329,365 )
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Child Health and Human Development Extramural Research	000	1	2/21/2022	NEW	$329,365
														Subtotal = $329,365

Grand Total All Awards = $1,314,167

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Molecular Mechanisms of Regeneration Termination

Award Number: R01HD108059

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer