Fat regulates expression of four-jointed reporters in vivo through a 20 bp element independently of the Hippo pathway.

Abstract Development of an organism requires accurate coordination between the growth of a tissue and orientation of cells within the tissue. The large cadherin Fat has been shown to play a role in both of these processes. Fat is involved in the establishment of planar cell polarity and regulates growth through the Hippo pathway, a developmental cascade that controls proliferation and apoptosis. Both Fat and the Hippo pathway are known to regulate transcription of four-jointed , although the nature of this regulation is unknown. In this study, we test whether Fat affects four-jointed transcription via or independently of Hippo pathway. Our analysis of the four-jointed regulatory region reveals a 1.2 kb element that functions as an enhancer for graded expression of Four-jointed in the eye imaginal disc. Within this enhancer element, we identify a 20 bp fragment that is critical for regulation by Fat but not by Hippo. Our findings suggest that Fat and the Hippo pathway control four-jointed expression independently of each other and none of the transcription factors known to function downstream of the Hippo pathway are required to regulate four-jointed expression through the 1.2 kb element. Highlights • Four-jointed genomic region contains a 1.2 kb eye enhancer located downstream of the coding region. • The eye enhancer is sensitive to Notch, WNT, JAK/STAT, Hippo, and Fat. • Fat controls the four-jointed eye enhancer through a 20 bp element. • Fat and Hippo response elements overlap, but are separable. [ABSTRACT FROM AUTHOR]