The Mango lab studies organ development and physiology using a simple organ, the C. elegans foregut, that nonetheless faces the same hurdles that confront organs in more complex animals. We combine molecular genetics, genomics and cell biological approaches to address three aspects of organogenesis:
Pluripotency and embryogenesis (reference 1): In early embryos, cells are born pluripotent, meaning they can adopt any cell fate. Over time, cells lose pluripotency and acquire a defined fate such as ‘foregut’. We have begun to explore the mechanisms that govern pluripotency and its loss in a developing embryo. We are particularly interested in the contribution of nuclear organization and chromatin architecture.
Transcriptional pathways for organ development (reference 2): The FoxA family of transcription factors establishes the foregut in all animals that have been examined, but the mechanisms are not well understood. In one project, we are studying how C. elegans PHA-4/FoxA controls transcription within a developing organ. Previously, we found that the DNA binding affinity of PHA-4 for its target genes influences the timing of target gene activation. In the future, we’d like to visualize the effects of affinity on DNA binding and promoter organization. In another project, we have screened for upstream regulators of pha-4 and discovered a cohort of novel but conserved genes that may be negative regulators of pha-4. Our continuing goal is to elucidate what these novel factors do in C. elegans and vertebrates.
Environmental Cues (reference 3). More recently, we have extended our studies to probe how the developmental pathways that govern gut development in embryos are redeployed after birth, to sense and respond to food availability.
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