Abstract
Snail (Sna) plays a pivotal role in epithelia-mesenchymal transition and cancer metastasis, yet its functions in normal tissue development remain elusive. Here, using Drosophila as a model organism, we identified Sna as an essential regulator of Hippo signalling-mediated cell proliferation and tissue growth. First, Sna is necessary and sufficient for impaired Hippo signalling-induced cell proliferation and tissue overgrowth. Second, Sna is necessary and sufficient for the expression of Hippo pathway target genes. Third, genetic epistasis data indicate Sna acts downstream of Yki in the Hippo signalling. Finally, Sna is physiologically required for tissue growth in normal development. Mechanistically, Yki activates the transcription of sna, whose protein product binds to Scalloped (Sd) and promotes Sd-dependent cell proliferation. Thus, this study uncovered a previously unknown physiological function of Sna in normal tissue development and revealed the underlying mechanism by which Sna modulates Hippo signalling-mediated cell proliferation and tissue growth.
Highlights
Tissue growth and organ size are controlled by coordinated regulation of cell number and cell size, while maintenance of cell number depends on the balance of cell death and proliferation
When the Hippo pathway is inactive, unphosphorylated Yki enters the nucleus to form a complex with the transcription factor Scalloped (Sd), which activates the expression of target genes involved in the control of cell growth, proliferation, survival and metabolism [5–7]
The depletion of hpo promoted cell proliferation in the corresponding region detected by increased anti-PH3 staining, which was dramatically suppressed by knocking-down sna and sd
Summary
Tissue growth and organ size are controlled by coordinated regulation of cell number and cell size, while maintenance of cell number depends on the balance of cell death and proliferation. The Hippo pathway, first identified in Drosophila, enables evolutionarily conserved signalling that regulates tissue growth and organ size in animal development [1]. When the Hippo pathway is inactive, unphosphorylated Yki enters the nucleus to form a complex with the transcription factor Scalloped (Sd), which activates the expression of target genes involved in the control of cell growth, proliferation, survival and metabolism [5–7]. More than 30 components/regulators of the Hippo pathway besides the core kinase cascade have been characterized over the past decade [12], additional factors that modulate Hippo signalling-mediated tissue growth remain to be elucidated. We identified Sna as a crucial modulator of Hippo signalling-mediated tissue growth in Drosophila development. Our results identified Sna as an essential regulator of the Hippo pathway and revealed the underlying mechanism by which Sna modulates Hippo signalling-mediated cell proliferation, tissue growth and tumour progression
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