The cell adhesion molecule Echinoid promotes tissue survival and separately restricts tissue overgrowth in imaginal discs.

The interactions that cells in imaginal discs have with their neighbors are known to regulate their ability to survive. In a screen of genes encoding cell surface proteins for gene knockdowns that affect the size or shape of mutant clones, we found that clones of cells with reduced levels of () are fewer, smaller, and can be eliminated during development. In contrast, discs composed mostly of mutant tissue are overgrown.

Coordinated growth of linked epithelia is mediated by the Hippo pathway.

An epithelium in a living organism seldom develops in isolation. Rather, most epithelia are tethered to other epithelial or non-epithelial tissues, necessitating growth coordination between layers. We investigated how two tethered epithelial layers of the larval wing imaginal disc, the disc proper (DP) and the peripodial epithelium (PE), coordinate their growth.

Ets21C sustains a pro-regenerative transcriptional program in blastema cells of Drosophila imaginal discs.

An important unanswered question in regenerative biology is to what extent regeneration is accomplished by the reactivation of gene regulatory networks used during development versus the activation of regeneration-specific transcriptional programs. Following damage, Drosophila imaginal discs, the larval precursors of adult structures, can regenerate missing portions by localized proliferation of damage-adjacent tissue. Using single-cell transcriptomics in regenerating wing discs, we have obtained a comprehensive view of the transcriptome of regenerating discs and identified two regeneration-specific cell populations within the blastema, Blastema1 and Blastema2.

Imaginal Disc Regeneration: Something Old, Something New.

Imaginal discs are simple epithelial sacs found in larvae, which generate adult structures including wings and legs. The first studies of imaginal disc regeneration involved technically challenging transplantation experiments. Yet despite the difficulty, many aspects of regeneration including wound healing, blastema formation, and the repatterning of regenerated tissue were characterized.

Single-cell transcriptomics of the wing disc reveals instructive epithelium-to-myoblast interactions.

In both vertebrates and invertebrates, generating a functional appendage requires interactions between ectoderm-derived epithelia and mesoderm-derived cells. To investigate such interactions, we used single-cell transcriptomics to generate a temporal cell atlas of the wing disc from two developmental time points. Using these data, we visualized gene expression using a multilayered model of the wing disc and cataloged ligand-receptor pairs that could mediate signaling between epithelial cells and adult muscle precursors (AMPs).

Membrane potential regulates Hedgehog signalling in the Drosophila wing imaginal disc.

While the membrane potential of cells has been shown to be patterned in some tissues, specific roles for membrane potential in regulating signalling pathways that function during development are still being established. In the Drosophila wing imaginal disc, Hedgehog (Hh) from posterior cells activates a signalling pathway in anterior cells near the boundary which is necessary for boundary maintenance. Here, we show that membrane potential is patterned in the wing disc.

The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary-like interactions at clone margins.

During development, tissue-specific patterns of gene expression are established by transcription factors and then stably maintained via epigenetic mechanisms. Cancer cells often express genes that are inappropriate for that tissue or developmental stage. Here, we show that high activity levels of Yki, the Hippo pathway coactivator that causes overgrowth in imaginal discs, can also disrupt cell fates by altering expression of selector genes like () and ().

Damage-responsive, maturity-silenced enhancers regulate multiple genes that direct regeneration in .

Like tissues of many organisms, imaginal discs lose the ability to regenerate as they mature. This loss of regenerative capacity coincides with reduced damage-responsive expression of multiple genes needed for regeneration. We previously showed that two such genes, and , are regulated by a single damage-responsive enhancer that becomes progressively inactivated via Polycomb-mediated silencing as discs mature (Harris et al.

Harnessing epithelial homeostatic mechanisms to fight cancer.

Cancer treatments have, in general, targeted the cancer cell itself. This approach has often been unsuccessful in the long term, especially for solid tumors. Even targeted therapies based on sequencing cancer genomes can be thwarted by genetic heterogeneity within tumors.

The BMP2/4 ortholog Dpp can function as an inter-organ signal that regulates developmental timing.

Developmental transitions are often triggered by a neuroendocrine axis and can be contingent upon multiple organs achieving sufficient growth and maturation. How the neurodendocrine axis senses the size and maturity of peripheral organs is not known. In larvae, metamorphosis is triggered by a sharp increase in the level of the steroid hormone ecdysone, secreted by the prothoracic gland (PG).

CtBP impedes JNK- and Upd/STAT-driven cell fate misspecifications in regenerating imaginal discs.

Regeneration following tissue damage often necessitates a mechanism for cellular re-programming, so that surviving cells can give rise to all cell types originally found in the damaged tissue. This process, if unchecked, can also generate cell types that are inappropriate for a given location. We conducted a screen for genes that negatively regulate the frequency of notum-to-wing transformations following genetic ablation and regeneration of the wing pouch, from which we identified mutations in the transcriptional co-repressor When CtBP function is reduced, ablation of the pouch can activate the JNK/AP-1 and JAK/STAT pathways in the notum to destabilize cell fates.

Ras Brakes for Hippo.

Normal organ growth requires precise signaling from key developmental pathways, as well as careful coordination between these pathways. In this issue of Developmental Cell, Pascual and colleagues (2017) investigate the dire consequences of simultaneous deregulation of both the Ras and Hippo pathways.

Imaginal disc regeneration takes flight.

Drosophila imaginal discs, the larval precursors of adult structures such as the wing and leg, are capable of regenerating after damage. During the course of regeneration, discs can sometimes generate structures that are appropriate for a different type of disc, a phenomenon termed transdetermination. Until recently, these phenomena were studied by physically fragmenting discs and then transplanting them into the abdomens of adult female flies.

Size regulation blossoms in Kobe.

Coincident with the blossoming of the sakura was the 14th annual CDB Symposium hosted by the RIKEN Center for Developmental Biology in Kobe, Japan. This year's meeting, 'Size in Development: Growth, Shape and Allometry' focused on the molecular and cellular mechanisms underlying differences in size and shape and how they have evolved. On display was the power of using diverse approaches ranging from the study of organoids to whole organisms.

Plexins function in epithelial repair in both Drosophila and zebrafish.

In most multicellular organisms, homeostasis is contingent upon maintaining epithelial integrity. When unanticipated insults breach epithelial barriers, dormant programmes of tissue repair are immediately activated. However, many of the mechanisms that repair damaged epithelia remain poorly characterized.

Persistence of RNAi-Mediated Knockdown in Drosophila Complicates Mosaic Analysis Yet Enables Highly Sensitive Lineage Tracing.

RNA interference (RNAi) has emerged as a powerful way of reducing gene function in Drosophila melanogaster tissues. By expressing synthetic short hairpin RNAs (shRNAs) using the Gal4/UAS system, knockdown is efficiently achieved in specific tissues or in clones of marked cells. Here we show that knockdown by shRNAs is so potent and persistent that even transient exposure of cells to shRNAs can reduce gene function in their descendants.

Localized epigenetic silencing of a damage-activated WNT enhancer limits regeneration in mature Drosophila imaginal discs.

Many organisms lose the capacity to regenerate damaged tissues as they mature. Damaged Drosophila imaginal discs regenerate efficiently early in the third larval instar (L3) but progressively lose this ability. This correlates with reduced damage-responsive expression of multiple genes, including the WNT genes wingless (wg) and Wnt6.

Progesterone regulates the proliferation of breast cancer cells - in vitro evidence.

Reports state that surgery performed at different phases of the menstrual cycle may significantly affect breast cancer treatment outcome. From previous studies, we identified differentially expressed genes in each menstrual cycle phase by microarray, then subjected them to functional in vitro analyses. Microarray studies disclosed genes that are upregulated in the luteal phase and follicular phase.

Organ Size Control: Lessons from Drosophila.

Of fundamental interest to biologists is how organs achieve a reproducible size during development. Studies of the developing Drosophila wing have provided many key insights that will help give a conceptual understanding of the process beyond the fly. In the wing, there is evidence for both "top-down" mechanisms, in which signals emanating from small subsets of cells direct global proliferation, and "bottom-up" mechanisms, in which the final size is an emergent property of local cell-cell interactions.

Indeterminate Growth: Could It Represent the Ancestral Condition?

Although we are used to the idea that many organisms stop growing when they reach a predictable size, in many taxa, growth occurs throughout the life of an organism, a phenomenon referred to as indeterminate growth. Our comparative analysis suggests that indeterminate growth may indeed represent the ancestral condition, whereas the permanent arrest of growth may be a more derived state. Consistent with this idea, in diverse taxa, the basal branches show indeterminate growth, whereas more derived branches arrest their growth.

Energy stress tames the Hippo pathway.

The kinase AMPK, a sensor of cellular energy stress, has been shown to oppose the growth-promoting activity of YAP, the transcriptional co-activator downstream of the Hippo signalling pathway. This finding may help to explain why the antidiabetic drug metformin, for which AMPK is a key effector, is linked to cancer-protective activity.

CoinFLP: a system for efficient mosaic screening and for visualizing clonal boundaries in Drosophila.

Screens in mosaic Drosophila tissues that use chemical mutagenesis have identified many regulators of growth and patterning. Many of the mutant phenotypes observed were contingent upon the presence of both wild-type and mutant cells in the same tissue. More recently, large collections of RNAi lines or cDNAs expressed under Gal4/UAS control have been used to alter gene expression uniformly in specific tissues.

Efficacy of Varunadi Ghritha (polyherbal compound) in treated head and neck cancer cases as a biological response modifier.

Background: Persistent immune suppression is reported in Head and Neck Cancers (HNC) even after treatment and a higher recurrence rate was observed in patients with poor CD3 count. Loco regional recurrences and second primary tumours are the common forms of failure in head and neck cancers. Several agents have been tried to overcome this problem without much benefit.

The Drosophila F-box protein Fbxl7 binds to the protocadherin fat and regulates Dachs localization and Hippo signaling.

The Drosophila protocadherin Fat (Ft) regulates growth, planar cell polarity (PCP) and proximodistal patterning. A key downstream component of Ft signaling is the atypical myosin Dachs (D). Multiple regions of the intracellular domain of Ft have been implicated in regulating growth and PCP but how Ft regulates D is not known.