RESUMO
BACKGROUND: During segmentation of the zebrafish embryo, inside-out signaling activates Integrin α5, which is necessary for somite border morphogenesis. The direct activator of Integrin α5 during this process is unknown. One candidate is Rap1b, a small monomeric GTPase implicated in Integrin activation in the immune system. RESULTS: Knockdown of rap1b, or overexpression of a dominant negative rap1b, causes a mild axis elongation defect in zebrafish. However, disruption of rap1b function in integrin α5(-/-) mutants results in a strong reduction in Fibronectin (FN) matrix assembly in the paraxial mesoderm and a failure in somite border morphogenesis along the entire anterior-posterior axis. Somite patterning appears unaffected, as her1 oscillations are maintained in single and double morphants/mutants, but somite polarity is gradually lost in itgα5(-/-) ; rap1b MO embryos. CONCLUSIONS: In itgα5(-) (/) (-) mutants, rap1b is required for proper somite border morphogenesis in zebrafish. The loss of somite borders is not a result of aberrant segmental patterning. Rather, somite boundary formation initiates but is not completed, due to the failure to assemble FN matrix along the nascent boundary. We propose a model in which Rap1b activates Integrin/Fibronectin receptors as part of an "inside-out" signaling pathway that promotes Integrin binding to FN, FN matrix assembly, and subsequent stabilization of morphological somite boundaries.
Assuntos
Fase de Clivagem do Zigoto/fisiologia , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Integrina alfa5/metabolismo , Transdução de Sinais/fisiologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Proteínas rap de Ligação ao GTP/metabolismo , Animais , Polaridade Celular/fisiologia , Técnicas de Silenciamento de Genes , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Hibridização In Situ , Integrina alfa5/genética , Microscopia de Fluorescência , Morfogênese/fisiologia , Morfolinos/genética , Somitos/embriologia , Proteínas rap de Ligação ao GTP/genéticaRESUMO
Overconfidence is a prevalent problem and it is particularly consequential in its relation with scientific knowledge: being unaware of one's own ignorance can affect behaviours and threaten public policies and health. However, it is not clear how confidence varies with knowledge. Here, we examine four large surveys, spanning 30 years in Europe and the United States and propose a new confidence metric. This metric does not rely on self-reporting or peer comparison, operationalizing (over)confidence as the tendency to give incorrect answers rather than 'don't know' responses to questions on scientific facts. We find a nonlinear relationship between knowledge and confidence, with overconfidence (the confidence gap) peaking at intermediate levels of actual scientific knowledge. These high-confidence/intermediate-knowledge groups also display the least positive attitudes towards science. These results differ from current models and, by identifying specific audiences, can help inform science communication strategies.
Assuntos
Comunicação , Teoria Ética , Humanos , Europa (Continente) , Conhecimento , AtitudeRESUMO
Dendrite arbor pattern determines the functional characteristics of a neuron. It is founded on primary branch structure, defined through cell intrinsic and transcription-factor-encoded mechanisms. Developing arbors have extensive acentrosomal microtubule dynamics, and here, we report an unexpected role for the atypical actin motor Myo6 in creating primary branch structure by specifying the position, polarity, and targeting of these events. We carried out in vivo time-lapse imaging of Drosophila adult sensory neuron differentiation, integrating machine-learning-based quantification of arbor patterning with molecular-level tracking of cytoskeletal remodeling. This revealed that Myo6 and the transcription factor Knot regulate transient surges of microtubule polymerization at dendrite tips; they drive retrograde extension of an actin filament array that specifies anterograde microtubule polymerization and guides these microtubules to subdivide the tip into multiple branches. Primary branches delineate functional compartments; this tunable branching mechanism is key to define and diversify dendrite arbor compartmentalization.
Assuntos
Dendritos/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Neurogênese , Animais , Linhagem Celular , Células Cultivadas , Dendritos/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Microtúbulos/metabolismo , Cadeias Pesadas de Miosina/genética , Fatores de Transcrição/metabolismoRESUMO
An important concept in ethology is that complex behaviors can be constructed from a set of basic motor patterns. Identifying the set of patterns available to an animal is key to making quantitative descriptions of behavior that reflect the underlying motor system organization. We addressed these questions in zebrafish larvae, which swim in bouts that are naturally segmented in time. We developed a robust and general purpose clustering method (clusterdv) to ensure accurate identification of movement clusters and applied it to a dataset consisting of millions of swim bouts, captured at high temporal resolution from a comprehensive set of behavioral contexts. We identified a set of thirteen basic swimming patterns that are used flexibly in various combinations across different behavioral contexts and show that this classification can be used to dissect the sensorimotor transformations underlying larval social behavior and hunting. Furthermore, using the same approach at different levels in the behavioral hierarchy, we show that the set of swim bouts are themselves constructed from a basic set of tail movements and that bouts are executed in sequences specific to different behaviors.