A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC)

Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between and a key tumor suppressor in colorectal cancer, we found that controls the levels of and that knock down of recapitulates phenotypes of impaired function including failed intestinal differentiation. Exogenous human rescued failed intestinal differentiation in zebrafish models of deficiency. Our data demonstrate a novel role for in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of .