ABSTRACT
The Hippo signaling pathway is widely considered a master regulator of organ growth because of the prominent overgrowth phenotypes caused by experimental manipulation of its activity. Contrary to this model, we show here that removing Hippo transcriptional output did not impair the ability of the mouse liver and Drosophila eyes to grow to their normal size. Moreover, the transcriptional activity of the Hippo pathway effectors Yap/Taz/Yki did not correlate with cell proliferation, and hyperactivation of these effectors induced gene expression programs that did not recapitulate normal development. Concordantly, a functional screen in Drosophila identified several Hippo pathway target genes that were required for ectopic overgrowth but not normal growth. Thus, Hippo signaling does not instruct normal growth, and the Hippo-induced overgrowth phenotypes are caused by the activation of abnormal genetic programs.
Subject(s)
Drosophila melanogaster , Eye , Gene Expression Regulation, Developmental , Hippo Signaling Pathway , Liver , Transcription, Genetic , Transcriptional Coactivator with PDZ-Binding Motif Proteins , YAP-Signaling Proteins , Animals , Mice , Drosophila melanogaster/embryology , Drosophila melanogaster/genetics , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Eye/embryology , Hippo Signaling Pathway/genetics , Liver/embryology , Organ Size , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Trans-Activators/genetics , Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism , YAP-Signaling Proteins/metabolismABSTRACT
We report on the evolution of ultrastructural modifications in bovine and rabbit corneal sections after in vitro swelling. The number of stromal fibers decreases with time during swelling. The fact that swelling occurs more rapidly in the center of a lamellae than near the interlamellar spaces indicates that there is a heterogeneous distribution of interfibrillar matrix components and that corneal inhibition mechanisms vary according to the number of lamellaes. The appearance during swelling of periodic striations of collagen fibers and of an irregular network constituted of filaments and granules in the interfibrillar spaces suggests that corneal collagen fibers are covered by a pleated proteoglycan-glycoportein substance that is unrolled during swelling. The filaments seem to be linked to collagen via dense granules located on fibers. The distance between the granules is 643 A. A definite correspondence between the distribution of these linking granules and the periodic striations of collagen cannot be determined. Other granules of undetermined chemical nature seem to link only filaments in the interfibrillar space.
