Yorkie controls tube length and apical barrier integrity during airway development

Abstract

Epithelial organ size and shape depend on cell shape changes, cell–matrix communication, and apical membrane growth. The Drosophila melanogaster embryonic tracheal network is an excellent model to study these processes. Here, we show that the transcriptional coactivator of the Hippo pathway, Yorkie (YAP/TAZ in vertebrates), plays distinct roles in the developing Drosophila airways. Yorkie exerts a cytoplasmic function by binding Drosophila Twinstar, the orthologue of the vertebrate actin-severing protein Cofilin, to regulate F-actin levels and apical cell membrane size, which are required for proper tracheal tube elongation. Second, Yorkie controls water tightness of tracheal tubes by transcriptional regulation of the δ-aminolevulinate synthase gene (Alas). We conclude that Yorkie has a dual role in tracheal development to ensure proper tracheal growth and functionality.

Form and function of the apical extracellular matrix: new insights from Caenorhabditis elegans, Drosophila melanogaster, and the vertebrate inner ear

“…Multiple aECM regulators are repressed by Blimp-1 25 , whose activity may be regulated by the feedback mechanism that regulates taenidial spacing 53 . The Hippo pathway transcription factor Yorkie (YAP/TAZ) has a dual role in tracheal morphogenesis, promoting tube elongation via the expression of cytoskeletal factors, and promoting water tightness via expression of the crosslinking enzyme Alas 26 . YAP/TAZ signaling may coordinate the regulation of tracheal cytoskeletal dynamics and the aECM.…”

The Molecular Network of YAP/Yorkie at the Cell Cortex and their Role in Ocular Morphogenesis

“…Recently, work from Skouloudaki et al, Xu et al, and Meyer et al showed that Yki in the Drosophila trachea/wing disc and YAP in murine hepatocytes are enriched in the apical F-actin area, where they interact with actin cytoskeleton molecules to regulate tissue morphogenesis [ 14 , 18 , 19 ]. More specifically, these groups found that Yki and YAP interact with actin cytoskeletal components, such as Twinstar (Tsr), Trio, Dia, and Cingulin.…”

“…More recent data have demonstrated a novel mechanism by which hepatocytes sense organ size during liver regeneration by means of changes in the apical actomyosin network that trigger YAP nuclear translocation [ 14 ]. The relationship of YAP/Yki and actin cytoskeleton is bidirectional, with studies indicating that the Hippo pathway regulates actin cytoskeleton in Drosophila [ 10 , 15 , 16 , 17 , 18 , 19 ]. Moreover, other groups have demonstrated the interaction of core Hippo pathway components, including Yki, with F-actin regulators [ 18 , 20 , 21 , 22 , 23 ].…”

“…The relationship of YAP/Yki and actin cytoskeleton is bidirectional, with studies indicating that the Hippo pathway regulates actin cytoskeleton in Drosophila [ 10 , 15 , 16 , 17 , 18 , 19 ]. Moreover, other groups have demonstrated the interaction of core Hippo pathway components, including Yki, with F-actin regulators [ 18 , 20 , 21 , 22 , 23 ]. Together, there is sufficient evidence to support that mechanical cues, sensed through the actin cytoskeleton at the epithelial cell apex, signal through YAP/Yki to promote organ growth and tissue homeostasis.…”

Developmental Regulation of Mitotic Chromosome Formation Revealed by Condensin Reporter Mice

“…To better understand the dynamic behaviour of Ncaph and Ncaph2 in live haematopoietic precursors, we used Fluorescence Correlation Spectroscopy (FCS). Due to the low incident light intensities used in FCS, it is a reasonably non-invasive method with single molecule sensitivity that allows the dynamic behaviour of fluorescent molecules (e.g., their molecular movement / diffusion) to be analysed in living cells at physiological concentrations [39][40][41][42][43][44] . In FCS, fluctuations in fluorescence intensity are recorded at high temporal resolution, and then used to infer the molecular movement of molecules entering or leaving a subfemtoliter detection volume ( Figure 4A).…”