A full understanding of embryonic endocrine pancreas development will be key to the establishment of islet replacement strategies. In particular, it is important to identify molecular pathways that establish the correct balance of specific endocrine pancreatic islet cell types. Recently, our work in the zebrafish has revealed that the correct ratio of ? and ? cell fates depends on the homeodomain transcription factor Mnx1 (Hb9); in the absence of functional Mnx1, ? cell precursors give rise to ? cells. ( 1) Our study suggests that mnx1 may function in ? cell precursors to suppress the ? cell fate. Here we consider how Mnx1 may interact with other endocrine-specific transcription factors to specify ? cells. Our work emphasizes the vital importance of Mnx1 for ? cell development, and suggests that identifying Mnx1 transcriptional targets in ? cell precursors may provide important new information of direct relevance to stem cell-based protocols to cure diabetes.