ABSTRACT
The Hippo pathway is a conserved and critical regulator of tissue growth. The FERM protein Expanded is a key signaling hub that promotes activation of the Hippo pathway, thereby inhibiting the transcriptional co-activator Yorkie. Previous work identified the polarity determinant Crumbs as a primary regulator of Expanded. Here, we show that the giant cadherin Fat also regulates Expanded directly and independently of Crumbs. We show that direct binding between Expanded and a highly conserved region of the Fat cytoplasmic domain recruits Expanded to the apicolateral junctional zone and stabilizes Expanded. In vivo deletion of Expanded binding regions in Fat causes loss of apical Expanded and promotes tissue overgrowth. Unexpectedly, we find Fat can bind its ligand Dachsous via interactions of their cytoplasmic domains, in addition to the known extracellular interactions. Importantly, Expanded is stabilized by Fat independently of Dachsous binding. These data provide new mechanistic insights into how Fat regulates Expanded, and how Hippo signaling is regulated during organ growth.
Subject(s)
Cell Adhesion Molecules , Drosophila Proteins , Drosophila melanogaster , Hippo Signaling Pathway , Membrane Proteins , Animals , Drosophila melanogaster/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Transcription Factors/metabolism , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolismABSTRACT
OBJECTIVE: To assess the feasibility of iPhone-based teleradiology as a potential solution for the diagnosis of acute cervico-dorsal spine trauma. MATERIALS AND METHODS: We have developed a solution that allows visualization of images on the iPhone. Our system allows rapid, remote, secure, visualization of medical images without storing patient data on the iPhone. This retrospective study is comprised of cervico-dorsal computed tomogram (CT) scan examination of 75 consecutive patients having clinically suspected cervico-dorsal spine fracture. Two radiologists reviewed CT scan images on the iPhone. Computed tomogram spine scans were analyzed for vertebral body fracture and posterior elements fractures, any associated subluxation-dislocation and cord lesion. The total time taken from the launch of viewing application on the iPhone until interpretation was recorded. The results were compared with that of a diagnostic workstation monitor. Inter-rater agreement was assessed. RESULTS: The sensitivity and accuracy of detecting vertebral body fractures was 80% and 97% by both readers using the iPhone system with a perfect inter-rater agreement (kappa:1). The sensitivity and accuracy of detecting posterior elements fracture was 75% and 98% for Reader 1 and 50% and 97% for Reader 2 using the iPhone. There was good inter-rater agreement (kappa: 0.66) between both readers. No statistically significant difference was noted between time on the workstation and the iPhone system. CONCLUSION: iPhone-based teleradiology system is accurate in the diagnosis of acute cervicodorsal spinal trauma. It allows rapid, remote, secure, visualization of medical images without storing patient data on the iPhone.
