Syd/JIP3 Controls Tissue Size by Regulating Diap1 Turnover Downstream of Yorkie/YA

How organisms control organ size is a fundamental question in developmental and regenerative biology. The underlaying mechanisms are not well defined. For instance, we don’t fully understand how cell proliferation and cell death are mechanistically integrated within tissues to generate stereotypic size and shape characteristics.
Using the developing Drosophila wing, we have identified the JNK interacting protein-3 (JIP3) as a size regulator. Mechanistic studies revealed that JIP3 acts downstream of Yorkie, a broadly conserved tissue size control molecule. Interestingly, JIP3 appears to play a dual role during wing development: one the one hand, JIP3 stabilizes Diap1, a cell survival and Yorkie target molecule. This provides robustness to Yorkie’s growth promoting program during the rapid tissue expansion phase. On the other hand, JIP3 transcription is developmentally downregulated later in development, promoting Diap1 rapid degradation and allowing cell death to occur. This provides a developmentally timed mechanism for counteracting Yorkie-mediated tissue growth.