Transcriptional regulation of the Hand1 gene in the developing mouse conceptus

The Hand1 gene encodes a basic helix-loop-helix transcription factor that is essential for heart, yolk sac and placental development in mouse. The Hand1 expression domain is highly restricted in all of these tissues. Gene expression in multiple tissues is frequently regulated by modular enhancers, as is the case for Drosophila Hand and mouse Hand2. Previous results in the Cross laboratory suggested that the mouse Hand1 intron contained cardiac-specific enhancer activity. A combination of comparative genomics, comparative expression analysis, and a knockout mouse model lacking the endogenous Hand1 intron were used to investigate this possibility. The evidence presented in this thesis suggests that the Hand1 intron does not contain cardiac-specific enhancer activity but may regulate Hand1 expression levels.