This core Hippo pathway integrates many upstream inputs, in particular from the apical scaffolds Expanded (Ex FRMD6), Merlin (Mer NF2 Hamaratoglu et al., 2006 Badouel et al., 2009 Yin et al., 2013), and Kibra (Kib KIBRA Baumgartner et al., 2010 Genevet et al., 2010 Yu et al., 2010) acting redundantly to recruit and activate the core kinases and to trap Yki in an inactive cortical compartment. Recent evidence points to a major role of the Hippo pathway in the biology of stem cells and as a tumor suppressor in many cancers ( Halder and Johnson, 2011 Yu and Guan, 2013 Meng et al., 2016). Mutations in hippo or warts lead to a stabilization of unphosphorylated Yki in the nucleus and overproliferation.

First identified using genetic screens in Drosophila melanogaster, the core Hippo pathway is composed of two cytoplasmic kinases, Hippo (MST1/2 in humans Harvey et al., 2003 Wu et al., 2003) and Warts (Wts LATS1/2), which act to phosphorylate and exclude out of the nucleus the transcription coactivator Yorkie (Yki YAP and TAZ). Hippo signaling represents one key pathway regulating tissue size and cell proliferation, in particular for epithelial tissues. Intercellular signaling pathways, and in particular their effects on the cell cycle and cell death programs, are key mediators to coordinate this harmonious growth. In animals, the fine regulation of cell numbers and cell size ensures that tissues and organs reach their correct size and shape to fulfill their function. We propose a model in which the spectrin cytoskeleton recruits Bbg to the cortex, where Bbg promotes actomyosin contractility to regulate epithelial tissue growth. We show that Bbg binds to and colocalizes tightly with the ОІ-heavyвЂ“Spectrin/Kst subunit at the apical cortex and promotes Yki activity, F-actin enrichment, and the phosphorylation of the myosin II regulatory light chain Spaghetti squash. bbg-mutant tissues are smaller, with fewer cells that are less apically constricted than normal. Looking for apical scaffolds regulating tissue growth, we describe that Drosophila melanogaster big bang (Bbg), a poorly characterized multi-PDZ scaffold, controls epithelial tissue growth without affecting epithelial polarity and architecture. Recent evidence has highlighted the intricate connections between the cytoskeleton and the regulation of the key growth control Hippo pathway. During development, cell numbers are tightly regulated, ensuring that tissues and organs reach their correct size and shape.

Bbg the fox in the forest