A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects.

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 res

SUBMITTER: Kathiriya IS 

PROVIDER: S-EPMC12811143 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature