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

The role of GATA3 in hemifacial microsomia

Award Number: R01DE033098
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

Group Awards By:

View Award Description

The role of GATA3 in hemifacial microsomia - Abstract Hemifacial microsomia (HFM) spans an array of human congenital craniofacial birth defect syndromes characterized by asymmetric malformation or underdevelopment of the orbits (maxilla and zygoma), mandible, outer and middle ear structures, craniofacial nerves and soft tissue structures. These elements are derived from cranial neural crest cells (NCCs) that populate the pharyngeal arches. HFM is the second most common facial birth defect behind cleft palate, though unlike cleft palate, very few genes have a proven association with HFM. One of the few genes found repeatedly in GWAS studies is the transcription factor GATA3, which is the basis of this proposal. We have recently shown that GATA3 is required for facial symmetry, as Gata3 mutant mouse embryos develop craniofacial defects resembling those seen in HFM, with one side more severely affected than the other. However, our preliminary data show that while Gata3 mutant mouse embryos have several changes in pharyngeal arch gene regulatory networks (GRNs), including expansion of Bmp4 expression and reduction in Fgf8 expression, these changes are bilateral. Further, it is not clear if these represent primary or secondary changes to GRNs and whether defects occur in NCCs before they reach the pharyngeal arches. We hypothesize that GATA3 is required for two specific aspects of facial development: 1) to ensure sufficient migrating NCCs reach the first arch; and 2) to repress Bmp4 expression in the arch ectoderm after NCC migration that would otherwise drive down Fgf8 expression and result in asymmetric jaw morphogenesis. To address these hypotheses, we will pursue three specific aims. In Aim 1, we will perform a detailed analysis of NCC migration, proliferation/cell death and later differentiation in Gata3 mutants. We will also assess if disruption of internal organ asymmetry randomizes sided defects in Gata3 mutants. In Aim 2, we will perform dual scRNA-seq/scATAC-seq (scMultiome) in wild type and Gata3 mutants to identify symmetric and asymmetric changes in gene expression. We will correlate this with chromatin accessibility changes and functionally analyze identified putative cis-regulatory elements in vivo. In Aim 3, we will reduce Bmpr1a expression or increase Fgf8 expression in the mandibular arch of Gata3 mutant embryos to determine if either approach can rescue the Gata3 mutant phenotype. Our long-term goal is to elucidate the basis of facial defects in the Gata3 mutant embryos and to identify the cue or cues that result in asymmetry. Such an understanding has the potential to substantially impact the quality of care for HFM patients and may potentially lead to avenues for future treatment regimens designed to improve differences associated with HFM.


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 = $349,188 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Oral Diseases and Disorders Research	000	3	1/14/2026	NON-COMPETING CONTINUATION	$349,188
														Subtotal = $349,188

Issue Date FY: 2025 ( Subtotal = $396,945 )
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Oral Diseases and Disorders Research	001	2	5/6/2025	NON-COMPETING CONTINUATION	$39,695
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Oral Diseases and Disorders Research	000	2	1/14/2025	NON-COMPETING CONTINUATION	$357,250
														Subtotal = $396,945

Issue Date FY: 2024 ( Subtotal = $341,353 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Oral Diseases and Disorders Research	000	1	2/29/2024	NEW	$341,353
														Subtotal = $341,353

Grand Total All Awards = $1,087,486

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The role of GATA3 in hemifacial microsomia

Award Number: R01DE033098

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer