Beth A Firulli, Chloe A Ferguson, Corrie de Gier-de Vries, Ram Podicheti, Douglas B Rusch, Vincent M Christoffels, Michael Rubart-von der Lohe, Anthony B Firulli
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引用次数: 0
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 in which we directly replaced the Hand1 exons and intron with those of Hand2. The results show that 2% of Hand1Hand2/Hand2 mice 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.
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Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community.
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