Summary RAS genes are frequently mutated in cancers, yet an effective treatment has not been developed. This is partly due to an incomplete understanding of signaling within Ras-related tumors. To address this, we performed a genetic screen in Drosophila, aiming to find mutations that cooperate with oncogenic Ras (RasV12) to induce tumor overgrowth and invasion. We identified fiery mountain (fmt), a regulatory subunit of the protein phosphatase 6 (PP6) complex, as a tumor suppressor that synergizes with RasV12 to drive JNK-dependent tumor growth and invasiveness. We show that Fmt negatively regulates JNK upstream of dTAK1. We further demonstrate that disruption of PpV, the catalytic subunit of PP6, mimics fmt loss of function induced tumorigenesis. Finally, Fmt synergizes with PpV to inhibit JNK-dependent tumor progression. Our data here further highlight the power of Drosophila as a model system to unravel molecular mechanisms that may be relevant to human cancer biology.

In spite of the diversity of possible biological forms observed in nature, a limited range of morphospace is frequently occupied for a given trait. Several mechanisms have been proposed to explain this bias in the distribution of phenotypes including selection, drift, and developmental constraints. Despite extensive work on phenotypic bias, the underlying developmental mechanisms explaining why particular regions of morphological space remain unoccupied are poorly understood. To address this issue, we studied the sex comb, a group of modified bristles used in courtship that shows marked morphological diversity among Drosophila species. In many Drosophila species including Drosophila melanogaster, the sex comb rotates 90°to a vertical position during development. Here we analyze the effect of changing D. melanogaster sex comb length on the process of rotation. We find that artificial selection changes the number of bristles per comb without a proportional change in the space available for rotation. As a result, when increasing sex comb length, rather than displaying a similar straight vertical shape observed in other Drosophila species, long sex combs bend because rotation is blocked by a neighboring row of bristles. Our results show ways in which morphologies that would be favored by natural selection are apparently impossible to achieve developmentally. These findings highlight the potential role of development in modifying selectable variation in the evolution of Drosophila sex comb length.

The morphogenesis of sex combs (SCs), a male trait in many species of fruit flies, is an excellent system in which to study the cell biology, genetics and evolution of a trait. In Drosophila melanogaster, where the incipient SC rotates from horizontal to a vertical position, three signal comb properties have been documented: length, final angle and shape (linearity). During SC rotation, in which many cellular processes are occurring both spatially and temporally, it is difficult to distinguish which processes are crucial for which attributes of the comb. We have used a novel approach combining simulations and experiments to uncover the spatio-temporal dynamics underlying SC rotation. Our results indicate that 1) the final SC shape is primarily controlled by the inhomogeneity of initial cell size in cells close to the immature comb, 2) the final angle is primarily controlled by later cell expansion and 3) a temporal sequence of cell expansion mitigates the malformations generally associated with longer rotated SCs. Overall, our work has linked together the morphological diversity of SCs and the cellular dynamics behind such diversity, thus providing important insights on how evolution may affect SC development via the behaviours of surrounding epithelial cells.

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La evolución de los cambios alométricos en las patas de las moscas de la fruta: una historia enraizada en la biología del desarrollo ABSTRACTAllometric studies measure the scaling changes between different body parts and these often have implications on understanding ecology and evolution. Although most work on allometry has described its importance during phenotypic evolution, few studies have focused on studying how entrenched developmental processes can affect allometric changes. To explore this problem, here we used the sex comb, a male-specific group of bristles with a spectacular morphological diversity among Drosophila species. By combining morphometric analysis in wild type and genetically perturbed Drosophila melanogaster and Drosophila species, we studied the allometric changes that occur in leg length and other bristle rows in concert with sex comb radiation. We show that bristledevelopmental processes are important for understanding the allometric changes of Drosophila first tarsal segments. Different lines of evidence suggest that a complicated interaction between bristle spacing and movement are crucial for understanding the evolution of allometry in this system. As a result, this work shows that although the emergence of a new trait, the sex comb, can modify the allometric relationships, there is a hierarchy of ancestral developmental processes with respect to how easily they can be modified. As a result, the interconnection of developmental processes can bias the direction of morphological changes.Keywords: rotation, sex combs, transverse rows. RESUMENLa alometría estudia los cambios de tamaño entre las diferentes partes del cuerpo de los seres vivos y sus implicaciones ecológicas y evolutivas. Aunque la mayoría de los estudios en esta área se han centrado en investigar la importancia de los cambios alométricos en la evolución fenótipica, pocos estudios han analizado como la interconexión de los diferentes procesos del desarrollo afectan dichos cambios de tamaño. Para investigar la relación entre los mecanismos de desarrollo y los cambios alométricos, utilizamos los peines sexuales de diferentes especies del género Drosophila. Dichas estructuras, constituidas por un grupo de sedas ubicadas en las patas anteriores de los machos, presentan una variedad morfológica sobresaliente durante la evolución. Por medio de análisis morfométricos entre diferentes especies de Drosophila, incluidas líneas de Drosophila melanogaster modificadas genéticamente, investigamos los cambios alométricos que ocurren en el tamaño de las patas y diferentes tipos de sedas como resultado de la radiación de los peines sexuales. En este trabajo presentamos evidencia que sugiere una interacción compleja entre los mecanismos del desarrollo encargados de definir la distancia entre las sedas y su movimiento. Además, mostramos que dichos mecanismos son fundamentales para entender cómo evoluciona la alometría en los segmentos tarsales. Aunque la emergencia de una nueva característica puede modificar las relaciones alométricas, los p...

Associate Editor: Graciela Bailliet.Citation/Citar este artículo como. Malagon JN. Dinámicas complejas en el desarrollo del primer segmento tarsal de Drosophila melanogaster. Acta biol.Colomb. 2016;21(3):495-500. DOI: http://dx.doi.org/10.15446/abc.v21n3.53778El tema de este artículo fue presentado en el V Simposio Colombiano de Biología Evolutiva organizado por la Red Colombiana de Biología Evolutiva (COLEVOL) y sometido por invitación de la revista Acta Biológica Colombiana con el fin de incentivar la investigación en el área de biología evolutiva. RESUMENLa interacción de grupos de genes, proteínas, y células es necesaria para el desarrollo de un organismo multicelular. Por tal motivo, la teoría de la complejidad puede ser una herramienta indispensable para entender cómo diversos procesos embriológicos y evolutivos suceden. Sin embargo, en la mayoría de los programas de investigación estas áreas permanecen aisladas. En un esfuerzo por crear un punto de integración entre el Evo-Devo y las ciencias de la complejidad, en este documento propongo que las dinámicas celulares de epitelios pueden tener comportamientos que se asemejan a los encontrados en sistemas complejos. Dichas dinámicas celulares, además de regular la densidad celular de los epitelios, pueden conferir alta evolucionabilidad a estos tejidos. Para lograr este objetivo, utilizo como sistema el desarrollo del primer segmento tarsal de las patas anteriores de Drosophila melanogaster. Primero doy un ejemplo en el cual dinámicas aleatorias a nivel celular pueden generar la emergencia de patrones organizados a nivel del tejido. En seguida muestro como la modificación de características morfológicas del epitelio puede generar dinámicas celulares altamente organizadas o por el contrario aleatorios. Como resultado, planteó que el desarrollo de los epitelios muestra rasgos de comportamientos complejos y propone que la retro-alimentación entre tensión mecánica y procesos celulares son básicos para entender cómo se desarrollan y evolucionan los organismos multicelulares. Estos estudios ponen en evidencia las bases mecánicas de procesos complejos que conectan diversos niveles de organización.Palabras clave: auto-organización, peines sexuales, rotación. ABSTRACTGene, protein and cell interactions are vital for the development of a multicellular organism. As a result, complexity theory can be a fundamental tool to understand how diverse developmental and evolutionary processes occur. However, in most scientific programs these two fields are separated. In an effort to create a connection between the Evo-devo and complexity science, this article shows how the cell dynamics of epithelia can display behaviours with similar features to complex systems. Here, I propose that these cell dynamics, in addition to control cell density in epithelia, can provide high evolvability to this type of tissue. To achieve this goal, I used a as a systems the development of Drosophila melanogaster front legs. First, I provide an example in which order at the tissue level emerge from a...