Development of Morphological Diversity of Dendrites in Drosophila by the BTB-Zinc Finger Protein Abrupt

Morphological diversity of dendrites contributes to specialized functions of individual neurons. In the present study, we examined the molecular basis that generates distinct morphological classes of Drosophila dendritic arborization (da) neurons. da neurons are classified into classes I to IV in order of increasing territory size and/or branching complexity. We found that Abrupt (Ab), a BTB-zinc finger protein, is expressed selectively in class I cells. Misexpression of ab in neurons of other classes directed them to take the appearance of cells with smaller and/or less elaborated arbors. Loss of ab functions in class I neurons resulted in malformation of their typical comb-like arbor patterns and generation of supernumerary branch terminals. Together with the results of monitoring dendritic dynamics of ab-misexpressing cells or ab mutant ones, all of the data suggested that Ab endows characteristics of dendritic morphogenesis of the class I neurons

Difference in Dachsous Levels between Migrating Cells Coordinates the Direction of Collective Cell Migration

細胞集団が移動方向を調節して組織を形作る、新しい仕組みを発見. 京都大学プレスリリース. 2017-09-12.In contrast to extracellular chemotactic gradients, how cell-adhesion molecules contribute to directing cell migration remains more elusive. Here we studied the collective migration of Drosophila larval epidermal cells (LECs) along the anterior-posterior axis and propose a migrating cell group-autonomous mechanism in which an atypical cadherin Dachsous (Ds) plays a pivotal role. In each abdominal segment, the amount of Ds in each LEC varied along the axis of migration (Ds imbalance), which polarized Ds localization at cell boundaries. This Ds polarity was necessary for coordinating the migratory direction. Another atypical cadherin, Fat (Ft), and an unconventional myosin Dachs, both of which bind to Ds, also showed biased cell-boundary localizations, and both were required for the migration. Altogether, we propose that the Ds imbalance within the migrating tissue provides the directional cue and that this is decoded by Ds-Ft-mediated cell-cell contacts, which restricts lamellipodia formation to the posterior end of the cell

Self-organizing Mechanism for Development of Space-filling Neuronal Dendrites

Neurons develop distinctive dendritic morphologies to receive and process information. Previous experiments showed that competitive dendro-dendritic interactions play critical roles in shaping dendrites of the space-filling type, which uniformly cover their receptive field. We incorporated this finding in constructing a new mathematical model, in which reaction dynamics of two chemicals (activator and suppressor) are coupled to neuronal dendrite growth. Our numerical analysis determined the conditions for dendritic branching and suggested that the self-organizing property of the proposed system can underlie dendritogenesis. Furthermore, we found a clear correlation between dendrite shape and the distribution of the activator, thus providing a morphological criterion to predict the in vivo distribution of the hypothetical molecular complexes responsible for dendrite elongation and branching

Multidendritic sensory neurons in the adult Drosophila abdomen: origins, dendritic morphology, and segment- and age-dependent programmed cell death

<p>Abstract</p> <p>Background</p> <p>For the establishment of functional neural circuits that support a wide range of animal behaviors, initial circuits formed in early development have to be reorganized. One way to achieve this is local remodeling of the circuitry hardwiring. To genetically investigate the underlying mechanisms of this remodeling, one model system employs a major group of <it>Drosophila </it>multidendritic sensory neurons - the dendritic arborization (da) neurons - which exhibit dramatic dendritic pruning and subsequent growth during metamorphosis. The 15 da neurons are identified in each larval abdominal hemisegment and are classified into four categories - classes I to IV - in order of increasing size of their receptive fields and/or arbor complexity at the mature larval stage. Our knowledge regarding the anatomy and developmental basis of adult da neurons is still fragmentary.</p> <p>Results</p> <p>We identified multidendritic neurons in the adult <it>Drosophila </it>abdomen, visualized the dendritic arbors of the individual neurons, and traced the origins of those cells back to the larval stage. There were six da neurons in abdominal hemisegment 3 or 4 (A3/4) of the pharate adult and the adult just after eclosion, five of which were persistent larval da neurons. We quantitatively analyzed dendritic arbors of three of the six adult neurons and examined expression in the pharate adult of key transcription factors that result in the larval class-selective dendritic morphologies. The 'baseline design' of A3/4 in the adult was further modified in a segment-dependent and age-dependent manner. One of our notable findings is that a larval class I neuron, ddaE, completed dendritic remodeling in A2 to A4 and then underwent caspase-dependent cell death within 1 week after eclosion, while homologous neurons in A5 and in more posterior segments degenerated at pupal stages. Another finding is that the dendritic arbor of a class IV neuron, v'ada, was immediately reshaped during post-eclosion growth. It exhibited prominent radial-to-lattice transformation in 1-day-old adults, and the resultant lattice-shaped arbor persisted throughout adult life.</p> <p>Conclusion</p> <p>Our study provides the basis on which we can investigate the genetic programs controlling dendritic remodeling and programmed cell death of adult neurons, and the life-long maintenance of dendritic arbors.</p

Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells

In vertebrates, newly emerging transformed cells are often apically extruded from epithelial layers through cell competition with surrounding normal epithelial cells. However, the underlying molecular mechanism remains elusive. Here, using phospho-SILAC screening, we show that phosphorylation of AHNAK2 is elevated in normal cells neighboring RasV12 cells soon after the induction of RasV12 expression, which is mediated by calcium-dependent protein kinase C. In addition, transient upsurges of intracellular calcium, which we call calcium sparks, frequently occur in normal cells neighboring RasV12 cells, which are mediated by mechanosensitive calcium channel TRPC1 upon membrane stretching. Calcium sparks then enhance cell movements of both normal and RasV12 cells through phosphorylation of AHNAK2 and promote apical extrusion. Moreover, comparable calcium sparks positively regulate apical extrusion of RasV12-transformed cells in zebrafish larvae as well. Hence, calcium sparks play a crucial role in the elimination of transformed cells at the early phase of cell competition

AIP1 and cofilin ensure a resistance to tissue tension and promote directional cell rearrangement

Cells must resist or release tension/compression when proliferating and moving during development. Here the authors show that AIP1, together with cofilin, promotes local actin turnover to regulate linkage between actomyosin and cell junctions and resist mechanical load imposed by tissue stretching

Coronin-1 promotes directional cell rearrangement in Drosophila wing epithelium

Directional cell rearrangement is a critical process underlying correct tissue deformation during morphogenesis. Although the involvement of F-actin regulation in cell rearrangement has been established, the role and regulation of actin binding proteins (ABPs) in this process are not well understood. In this study, we investigated the function of Coronin-1, a WD-repeat actin-binding protein, in controlling directional cell rearrangement in the Drosophila pupal wing. Transgenic flies expressing Coronin-1-EGFP were generated using CRISPR-Cas9. We observed that Coronin-1 localizes at the reconnecting junction during cell rearrangement, which is dependent on actin interacting protein 1 (AIP1) and cofilin, actin disassemblers and known regulators of wing cell rearrangement. Loss of Coronin-1 function reduces cell rearrangement directionality and hexagonal cell fraction. These results suggest that Coronin-1 promotes directional cell rearrangement via its interaction with AIP1 and cofilin, highlighting the role of ABPs in the complex process of morphogenesis. Key words: morphogenesis, cell rearrangement, actin binding proteins (ABPs

Effects of glucose-insulin infusion during major oral and maxillofacial surgery on postoperative complications and outcomes

Abstract Background Secretion of hormones, which antagonize the action of insulin, is facilitated in response to surgery, and acute resistance to the action of insulin develops. Our aim is to elucidate the effects of intraoperative glycemic control by glucose-insulin (GI) infusion on postoperative complications and outcomes in major oral and maxillofacial surgery. Findings Thirty patients aged ≥ 60 years undergoing a radical operation of oral malignant tumors with tissue reconstruction (≥ 8 h) were analyzed. In the GI group, regular insulin was continuously applied with glucose-added acetate Ringer’s solution (5–10 g glucose per 500 mL). Blood glucose was adjusted within the target concentration of 80–120 mg/dL. In the control group, combination of acetate Ringer’s solution containing 1% (W/V) glucose and lactate Ringer’s solution, which contains no glucose, was employed. Perioperative clinical parameters, incidence of hypoalbuminemia, and postoperative complications, i.e., surgical site infection, necrosis of a reconstructed flap, bacteremia, hypotension, or pneumonia, were compared. Both serum total protein and albumin concentrations (postoperative day 1 [Day1]) were higher in the GI group. The mean infusion rate of glucose during surgery (mg/kg/h) was independently associated with the decrease in both serum total protein and albumin concentrations from the control to Day1. No difference was found between the groups in the incidence of postoperative complications and the days required until discharge, except less incidence of hypoalbuminemia in the GI group. Conclusions Application of additional glucose during major oral and maxillofacial surgery preserved serum albumin concentration. However, it did not lead to less postoperative complications and less days until discharge

Image-based parameter inference for epithelial mechanics.

Measuring mechanical parameters in tissues, such as the elastic modulus of cell-cell junctions, is essential to decipher the mechanical control of morphogenesis. However, their in vivo measurement is technically challenging. Here, we formulated an image-based statistical approach to estimate the mechanical parameters of epithelial cells. Candidate mechanical models are constructed based on force-cell shape correlations obtained from image data. Substitution of the model functions into force-balance equations at the cell vertex leads to an equation with respect to the parameters of the model, by which one can estimate the parameter values using a least-squares method. A test using synthetic data confirmed the accuracy of parameter estimation and model selection. By applying this method to Drosophila epithelial tissues, we found that the magnitude and orientation of feedback between the junction tension and shrinkage, which are determined by the spring constant of the junction, were correlated with the elevation of tension and myosin-II on shrinking junctions during cell rearrangement. Further, this method clarified how alterations in tissue polarity and stretching affect the anisotropy in tension parameters. Thus, our method provides a novel approach to uncovering the mechanisms governing epithelial morphogenesis