Two distinct waves of transcriptome and translatome changes drive Drosophila germline stem cell differentiation.

The tight control of fate transitions during stem cell differentiation is essential for proper tissue development and maintenance. However, the challenges in studying sparsely distributed adult stem cells in a systematic manner have hindered efforts to identify how the multilayered regulation of gene expression programs orchestrates stem cell differentiation in vivo. Here, we synchronised Drosophila female germline stem cell (GSC) differentiation in vivo to perform in-depth transcriptome and translatome analyses at high temporal resolution.

Programmed disassembly of a microtubule-based membrane protrusion network coordinates 3D epithelial morphogenesis in Drosophila.

Comprehensive analysis of cellular dynamics during the process of morphogenesis is fundamental to understanding the principles of animal development. Despite recent advancements in light microscopy, how successive cell shape changes lead to complex three-dimensional tissue morphogenesis is still largely unresolved. Using in vivo live imaging of Drosophila wing development, we have studied unique cellular structures comprising a microtubule-based membrane protrusion network.

Coordination of tissue homeostasis and growth by the Scribble-α-Catenin-Septate junction complex.

Maintaining apicobasal polarity (ABP) is crucial for epithelial integrity and homeostasis during tissue development. Although intracellular mechanisms underlying ABP establishment have been well studied, it remains to be addressed how the ABP coordinates tissue growth and homeostasis. By studying Scribble, a key ABP determinant, we address molecular mechanisms underlying ABP-mediated growth control in the wing imaginal disc.

Simultaneous activation of Tor and suppression of ribosome biogenesis by TRIM-NHL proteins promotes terminal differentiation.

Tissue development and homeostasis depend on the balance between growth and terminal differentiation, but the mechanisms coordinating these processes remain elusive. Accumulating evidence indicates that ribosome biogenesis (RiBi) and protein synthesis, two cellular processes sustaining growth, are tightly regulated and yet can be uncoupled during stem cell differentiation. Using the Drosophila adult female germline stem cell and larval neuroblast systems, we show that Mei-P26 and Brat, two Drosophila TRIM-NHL paralogs, are responsible for uncoupling RiBi and protein synthesis during differentiation.

Scribble and α-Catenin cooperatively regulate epithelial homeostasis and growth.

Epithelial homeostasis is an emergent property of both physical and biochemical signals emanating from neighboring cells and across tissue. A recent study reveals that Scribble, an apico-basal polarity determinant, cooperates with α-Catenin, an adherens junction component, to regulate tissue homeostasis in the wing imaginal disc. However, it remains to be addressed whether similar mechanisms are utilized in vertebrates.

Large Drosophila germline piRNA clusters are evolutionarily labile and dispensable for transposon regulation.

PIWI proteins and their guiding Piwi-interacting small RNAs (piRNAs) are crucial for fertility and transposon defense in the animal germline. In most species, the majority of piRNAs are produced from distinct large genomic loci, called piRNA clusters. It is assumed that germline-expressed piRNA clusters, particularly in Drosophila, act as principal regulators to control transposons dispersed across the genome.

Coupling between dynamic 3D tissue architecture and BMP morphogen signaling during wing morphogenesis.

At the level of organ formation, tissue morphogenesis drives developmental processes in animals, often involving the rearrangement of two-dimensional (2D) structures into more complex three-dimensional (3D) tissues. These processes can be directed by growth factor signaling pathways. However, little is known about how such morphological changes affect the spatiotemporal distribution of growth factor signaling.

Scribbled Optimizes BMP Signaling through Its Receptor Internalization to the Rab5 Endosome and Promote Robust Epithelial Morphogenesis.

Epithelial cells are characterized by apical-basal polarity. Intrinsic factors underlying apical-basal polarity are crucial for tissue homeostasis and have often been identified to be tumor suppressors. Patterning and differentiation of epithelia are key processes of epithelial morphogenesis and are frequently regulated by highly conserved extrinsic factors.

Adaptive protein divergence of BMP ligands takes place under developmental and evolutionary constraints.

The bone morphogenetic protein (BMP) signaling network, comprising evolutionary conserved BMP2/4/Decapentaplegic (Dpp) and Chordin/Short gastrulation (Sog), is widely utilized for dorsal-ventral (DV) patterning during animal development. A similar network is required for posterior crossvein (PCV) formation in the Drosophila pupal wing. Although both transcriptional and post-transcriptional regulation of co-factors in the network gives rise to tissue-specific and species-specific properties, their mechanisms are incompletely understood.

Transmembrane domain is crucial to the subcellular localization and function of Myc target 1.

Deregulation of c-MYC occurs in a variety of human cancers. Overexpression of c-MYC promotes cell growth, proliferation, apoptosis, transformation and genomic instability. MYC target 1 (MYCT1) is a direct target gene of c-MYC, and its murine homologue MT-MC1 recapitulated multiple c-Myc-related phenotypes.

Lithium down-regulates histone deacetylase 1 (HDAC1) and induces degradation of mutant huntingtin.

Lithium is an effective mood stabilizer that has been clinically used to treat bipolar disorder for several decades. Recent studies have suggested that lithium possesses robust neuroprotective and anti-tumor properties. Thus far, a large number of lithium targets have been discovered.

Dynamic change of TNIK in response to tumor necrosis factor alpha in a TRAF2-dependent manner.

TNIK (TRAF2- and NCK-interacting kinase) was named because of its association with TRAF2 (tumor necrosis factor receptor-associated factor 2). But the relationship between TNIK and TRAF2 is still elusive, in addition to which the involvement of TNIK in JNK activation by TNFα hints that there maybe a linkage between TNIK and TRAF2. In this work, we illustrated that TNIK protein levels were dynamic in response to TNFα stimulation in an ubiquitin-dependent manner.

Enormous influence of TNIK knockdown on intracellular signals and cell survival.

Basic cellular activities and coordinated cell actions are governed by intracellular signals, among which the Wnt signaling cascade plays an important role in tissue polarity and cell adhesion or movement through the activation of c-Jun N-terminal kinase (JNK) pathway. As one of the central transcriptional factors, Traf2- and Nck-interacting kinase (TNIK) mediates the transactivation of Wnt target genes and promotes the activity of c-Jun N-terminus kinase (JNK)2 when overexpressed. To further understand the function of TNIK, changes in intracellular signals were detected in colon cancer cell lines using a knockdown strategy.

Augmenting the antitumor effect of TRAIL by SOCS3 with double-regulated replicating oncolytic adenovirus in hepatocellular carcinoma.

Aberrant JAK/STAT3 pathway has been reported to be related to hepatocellular carcinoma (HCC) in many cell lines. In this study, a double-regulated oncolytic adenovirus vector that can replicate and induce a cytopathic effect in alpha-fetoprotein (AFP)-positive HCC cell lines with p53 dysfunction was successfully constructed. Two therapeutic genes, suppressor of cytokine signaling 3 (SOCS3) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were chosen and incorporated into this vector system, respectively.