Development. 2025 Sep 17:dev.204963. doi: 10.1242/dev.204963. Online ahead of print.
ABSTRACT
The bHLH transcription factors HAND1 and HAND2 are expressed in partially overlapping patterns during development. Studies have established evidence for significant functional redundancy between HAND1 and HAND2. To test redundancy fully, we engineered a Hand1 allele where we directly replace the Hand1 exons and intron with those of Hand2. Results show that 2% of Hand1Hand2/Hand2mice are viable and fertile. The remaining Hand1Hand2/Hand2 embryos exhibit neonatal lethality due to omphalocele accompanied by ventricular septal defects and conduction anomalies. Omphalocele can occur due to altered gut rotation. Our transcriptomic expression analysis reveals that established gene expression patterns associated with normal gut rotation are compromised. Interrogation of cardiac function in surviving Hand1Hand2/Hand2 mice reveals QRS abnormalities and cardiac morphogenic defects. These data support previous findings that HAND factors exhibit extensive functional overlap but also reveals that HAND1 protein has unique functions within the Hand1 expression domain and is required for normal embryonic development.
PMID:40960281 | DOI:10.1242/dev.204963
