Journal article
A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects
Nature cardiovascular research, v 5(1), pp 67-83
01 Jan 2026
PMID: 41461901
Abstract
Failure of septation of the interventricular septum (IVS) is the most common congenital heart defect, but mechanisms for patterning the IVS are largely unknown. Here we show that a Tbx5
/Mef2cAHF
progenitor lineage forms a compartment boundary bisecting the IVS. This coordinated population originates at a first and second heart field interface. Ablation of Tbx5
/Mef2cAHF
progenitors causes IVS disorganization, right ventricular hypoplasia and mixing of IVS lineages. Reduced dosage of the congenital heart defect transcription factor TBX5 disrupts boundary position and integrity, resulting in ventricular septation defects and patterning defects, including misexpression of Slit2 and Ntn1, which encode guidance cues. Reducing NTN1 dosage partly rescues cardiac defects in Tbx5 mutant embryos. Loss of Slit2 or Ntn1 causes ventricular septation defects and perturbed septal lineage distributions. Thus, we identify Tbx5 as a candidate selector gene, directing progenitors and regulating essential cues, to pattern a compartment boundary for proper cardiac septation, revealing mechanisms for cardiac birth defects.
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Details
- Title
- A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects
- Creators
- Irfan S Kathiriya (Corresponding Author) - University of California, San FranciscoMartin H Dominguez - Drexel UniversityKavitha S Rao - Gladstone InstitutesJonathon M Muncie-Vasic - Gladstone InstitutesW Patrick Devine - Gladstone InstitutesKevin M Hu - Creighton UniversitySwetansu K Hota - Gladstone InstitutesBayardo I Garay - University of California, San FranciscoDiego Quintero - Gladstone InstitutesPiyush Goyal - Gladstone InstitutesMegan N Matthews - California Institute of TechnologyReuben Thomas - Gladstone InstitutesTatyana Sukonnik - Gladstone InstitutesDario Miguel-Perez - Gladstone InstitutesSarah Winchester - Gladstone InstitutesEmily F Brower - Gladstone InstitutesAndré Forjaz - Johns Hopkins UniversityPei-Hsun Wu - Johns Hopkins UniversityDenis Wirtz - Johns Hopkins UniversityAshley L Kiemen - Johns Hopkins UniversityBenoit G Bruneau - Gladstone Institutes
- Publication Details
- Nature cardiovascular research, v 5(1), pp 67-83
- Publisher
- Nature Publishing
- Grant note
- UM1HL098179 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) K99 HL177318 / NHLBI NIH HHS UG3 CA275681 / NCI NIH HHS R01 CA300052 / NCI NIH HHS C06 RR018928 / NCRR NIH HHS UM1 HL098179 / NHLBI NIH HHS U54 CA268083 / NCI NIH HHS F32 HL162450 / NHLBI NIH HHS 1R56HL166894-01A1 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HL114948 / U.S. Department of Health & Human Services | National Institutes of Health (NIH)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001650273700001
- Scopus ID
- 2-s2.0-105026465627
- Other Identifier
- 991022196570604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems