Mouse Developmental Genetics and Transcription; uses molecular genetics to understand the mechanisms underlying developmental determination during mammalian embryogenesis. We employ molecular genetics to investigate the basic mechanisms underlying developmental determination during mammalian embryogenesis. Variation in the activity and abundance of transcription factors is widely acknowledged to be a regulatory nexus where signal cascades converge and are transduced into specific cellular responses. Regulation of the transcriptional apparatus is instructed through DNA:protein interactions mediated by specific transcription factors and accessory proteins. The underlying question we address is: how are tissues and organs generated, and how are they instructed to fulfil their differentiated fates? This most basic question can be dissected into components by addressing the multiple activities of individual transcription factor proteins and their genes. How do tissue-restricted transcription factors mediate such an enormous diversity of potential responses, and how do their aberrant responses lead to human cancer and congenital disease? Our approach to these conundrums all employ mouse germ line gene manipulation. Our studies have led to fascinating insights into the developmental origin of, and elaboration of differentiated function in, the central and peripheral nervous system, the kidney, the cardiovascular system and blood. We also continue to explore the molecular basis of human beta-globin gene regulation, as it comprises one of the most sophisticated models for chromatin-modulated gene regulatory complexity.