Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Molecular drivers of tissue-specific morphogenetic programs

Award Number: R01HD104784
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: 06/22/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

Group Awards By:

View Award Description

Molecular drivers of tissue-specific morphogenetic programs - Project summary Congenital malformations, or birth defects, are the leading cause of death of American children under the age of nine. Neural tube defects (NTDs) are among the most common and devastating congenital malformations, and result from a failure of the neural tube to close during early embryonic development. Neural tube closure requires not only that the paired neural folds raise and fuse together, but also that the neuroectoderm (precursor to the neural tube), narrows sufficiently for the neural folds to meet along the midline. This critical narrowing begins during gastrulation and is coupled to a concurrent anteroposterior (AP) extension of the neuroectoderm that results from the polarized rearrangement of cells into a longer and narrower array. This process, appropriately termed convergence & extension (C&E), is a highly conserved morphogenetic mechanism with essential roles in shaping numerous embryonic tissues and establishing the animal body plan. Neural tube closure and extension of the primary AP embryonic axis are driven by C&E of both the neuroectoderm and the underlying mesoderm, each of which exhibits a distinct suite of cell behaviors and contributes actively to axis extension. It remains poorly understood, however, how tissue identity is coordinated with tissue-specific cell behavior programs. Here, we address the tissue-specific morphogenesis underlying axis extension in zebrafish, a model vertebrate embryo. We recently reported that the TGF- family morphogen Nodal is not only necessary for C&E gastrulation movements in zebrafish, but also sufficient to promote these cell behaviors in otherwise naïve zebrafish embryonic explants. By varying the method of Nodal signaling activation, we can drive tissue- specific C&E of either the neuroectoderm or mesoderm within these explants. Importantly, this allows us to uncouple morphogenesis of individual tissue layers and distinguish the mechanisms that control cell identity from those that control cell movement. Each mode of C&E is associated with a specific developmental peak of Nodal activity and transcriptional profile, leading us to hypothesize that temporal patterns of Nodal activity define tissue-specific morphogenesis via distinct downstream molecular programs. Using cutting-edge optogenetic approaches to precisely manipulate Nodal activity, experiments proposed in Aim 1 will test how variations in temporal signaling dynamics control tissue-specific C&E both in and ex vivo. In Aims 2 and 3, we will define the specific components of each Nodal-dependent gene expression program that are necessary and/or sufficient for tissue-specific C&E of the mesoderm and neuroectoderm, respectively. This proposal leverages the unique advantages of our innovative explant model and optogenetic approaches to identify genes with novel roles in axis extension, thereby advancing a fundamental understanding of neural tube closure essential for improved diagnosis, prevention, and treatment strategies for NTDs.


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: 2026 ( Subtotal = $443,501 )
2026	2026	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	5	3/20/2026	NON-COMPETING CONTINUATION	$443,501
														Subtotal = $443,501

Issue Date FY: 2025 ( Subtotal = $443,501 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	4	4/2/2025	NON-COMPETING CONTINUATION	$443,501
														Subtotal = $443,501

Issue Date FY: 2024 ( Subtotal = $439,064 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	3	3/22/2024	NON-COMPETING CONTINUATION	$399,151
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	3	5/3/2024	NON-COMPETING CONTINUATION	$39,913
														Subtotal = $439,064

Issue Date FY: 2023 ( Subtotal = $443,501 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	2	3/15/2023	NON-COMPETING CONTINUATION	$443,501
														Subtotal = $443,501

Issue Date FY: 2022 ( Subtotal = $443,501 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	1	6/21/2022	NEW	$443,501
														Subtotal = $443,501

Grand Total All Awards = $2,213,068

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Molecular drivers of tissue-specific morphogenetic programs

Award Number: R01HD104784

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: 06/22/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer