The epithelial-mesenchymal transition of theDrosophilamesoderm requires the Rho GTP exchange factor Pebble

Abstract

the lateral edges of the mesoderm extend numerous protrusions. In pbl mutant embryos, however, cells appear more tightly adhered to their neighbours and extend very few protrusions. Consistent with the dependence of the mesoderm EMT and cytokinesis on actin organisation, the GTP exchange function of the PBL RhoGEF is required for both processes. By contrast, the N-terminal BRCT domains of PBL are required only for the cytokinetic function of PBL. These studies reveal that a novel PBL-mediated intracellular signalling pathway operates in mesodermal cells during the transition from an epithelial to migratory mesenchymal morphology during gastrulation.

Epithelial to Mesenchymal Transition in Human Skin Wound Healing Is Induced by Tumor Necrosis Factor-α through Bone Morphogenic Protein-2

“…Further, the Toll/Dorsal system is applied in both embryonic development and innate immunity in the wound healing of adult fly. 17,23 Thus, evolutionary conservation and functional redundancy implies the role of innate immunity in controlling EMT during wound healing. One end point of the Toll/Dorsal genetic pathway in drosophila is decapentaplegic (Dmel/dpp), which is orthologically related to BMP or TGF-␤.…”

The roles of CUX1 homeodomain proteins in the establishment of a transcriptional program required for cell migration and invasion

“…18 While Ect2 is known to play a role in mitosis, its ortholog Pebble has been shown to regulate cell migration and epithelial-mesenchymal transition, highlighting again the inter-relationship between these two cellular processes. 23,24 The importance of transcriptional regulation for Rho GTPases activity was confirmed both from siRNA-mediated knockdown of CUX1 as well as overexpression of p110 CUX1. Stable knockdown of CUX1 in two cell lines caused a reduction in the activity of RhoA, Cdc42 and Rac1.…”

Regulation of the Rac GTPase pathway by the multifunctional Rho GEF Pebble is essential for mesoderm migration in theDrosophilagastrula

“…RhoGEF2 and Rho1 promote the recruitment and assembly of cytoplasmic myosin that drives apical constriction during ventral furrow formation (Barrett et al, 1997;Hacker and Perrimon, 1998;Nikolaidou and Barrett, 2004;Dawes-Hoang et al, 2005). Another GEF called Pebble (Pbl) is indispensable for Htl-triggered cell shape changes and thus represents an excellent candidate that links FGF signalling to the modulation of cell shape (Schumacher et al, 2004;Smallhorn et al, 2004).…”