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Title: Mechanisms of restricted activation of the Torso receptor: from the eggshell to the embryo
Author: Mineo, Alessandro
Director/Tutor: Furriols Espona, Marc
Casanova i Roca, Jordi, 1959-
Keywords: Receptors cel·lulars
Cell receptors
Issue Date: 24-Nov-2016
Publisher: Universitat de Barcelona
Abstract: [eng] The establishment of the embryonic axis in the Drosophila embryo relies on four maternal systems. Anterior and posterior axes rely on morphogens located at the poles that will generate a gradient of activity along the embryo. In contrast, terminal and dorsoventral system rely on cues that are generated by follicle cells in the egg chamber to induce the restricted activation of their receptors, Torso and Toll respectively. In the case of the terminal signaling, the torso (tor) gene encodes for a tyrosine kinase receptor uniformly localised all around the membrane of the embryo but exclusively activated at the poles upon the activity of the Torso-like (Tsl) protein. Restricted activation of the Torso receptor at the embryonic poles relies on the tsl gene. Indeed, Tsl is expressed at the poles of the egg chamber during oogenesis and, in embryogenesis, accumulates at both poles of the inner side of the vitelline membrane, the innermost eggshell layer, by means of three protein encoded by the Nasrat (f(s) N), Polehole (f(s) Ph) and Closca (clos) genes. f(s) N, f(s) Ph and clos encode for proteins that localise in the vitelline membrane and are involved in the crosslinking of the vitelline membrane converting the eggshell into a stiff and insoluble layer. Indeed, females bearing mutations in any of these genes produce collapsed eggs due to defects in their eggshell. fs(1)N12, fs(1)ph1901 and clos1 are the only point mutation alleles which do not abolish the integrity of the vitelline membrane but cause the lack of terminal structures. The main objective of this work was to shed light on the role of Tsl, Nasrat, Polehole and Closca in ensuring restricted of Tor activation at the embryonic poles. In the case of Tsl, we found that, during oogenesis, it accumulates at the vitelline membrane while, in embryogenesis it localises at both ends of the embryonic plasma membrane probably at egg activation. These results suggest a a mechanism to transfer the Tsl from the egg chamber to the early embryo. This mechanism relies on the initial anchoring of Tsl at the vitelline membrane as it is secreted by the follicle cells, followed by its later translocation to the egg plasma membrane. In the case of Nasrat, Polehole and Closca,we found that embryo laid by fs(1)N12, fs(1)ph1901 and clos1 mutant females display defects in dorsoventral patterning specification besides their terminal phenotype. Nasrat, Polehole and Closca, are required for proper anchorage and activity of Nudel, a protease acting both in embryonic dorsoventral patterning and vitelline membrane integrity, thus providing a mechanism for the role of Nasrat, Polehole and Closca in vitelline membrane cross linking and dorsoventral patterning. Therefore, the dorsoventral and terminal systems, hitherto considered independent, share a common extracellular mechanism constituted by the Nasrat, Polehole and Closca proteins. Moreover, we found that these proteins have a new Tsl-independent role in terminal signaling. In the embryonic terminal system, Tor is activated only at the poles by its ligand Trunk while, in Drosophila larvae, Tor is also expressed and activated by another ligand called Prothoracicotropic hormone (PTTH) in the Prothoracic Gland. Ectopic expression of PTTH in the embryo is able to activate Tor ectopically even in the absence of Tsl but requires Nasrat, Polehole and Closca. From these results, we propose that a Nasrat/Polehole/Closca complex acts as a multifunctional hub to anchor various proteins synthesized at oogenesis, ensuring their spatial and temporal restricted function. These findings shed light on the eggshell not just as protective layer but as a specialised extracellular matrix that regulates the spatial and temporal control of early embryonic developmental processes.
[spa] El eje antero-posterior del embrión de Drosophila se especifica por acción de tres sistemas maternos: el sistema anterior, el sistema posterior y el sistema terminal. En el sistema terminal el receptor tirosina quinasa Torso (Tor) está localizado uniformemente en la membrana del embrión temprano pero se activa sólo en los polos por acción de la proteína Torso-like (Tsl). Aunque el papel de Tsl en la activación de Tor no está del todo claro, se ha descrito que Tsl es la única proteína de todo el sistema terminal localizada en los polos. De hecho, Tsl se acumula en la cara interna de la membrana vitelina (MV), anclado a las proteínas Nasrat, Polehole y Closca. El papel molecular de estas proteínas es poco conocido, pero análisis genéticos han demostrado que se necesitan para una correcta estructura de la MV y también para la activación de Tor. En esta tesis, nos hemos focalizado en la función de las proteínas Tsl, Nasrat, Polehole y Closca y su papel en la activación de Tor en los polos. Respecto a Tsl, descubrimos que esta proteína se acumula en la MV durante la oogénesis y, al principio de la embriogénesis, transloca de la MV a la membrana plasmática del embrión. En cuanto a Nasrat, Polehole y Closca descubrimos que estas proteínas se necesitan también para la correcta localización y función de Nudel, una proteína involucrada en la especificación del eje dorso ventral del embrión. Además encontramos que Nasrat, Polehole y Closca tienen una función adicional en el sistema terminal independiente de Tsl. De los resultados aquí descritos proponemos que un complejo formado por las proteínas Nasrat, Polehole y Closca podría funcionar en la MV como un centro multifuncional para anclar proteínas importantes por la especificación de los ejes del embrión.
Appears in Collections:Tesis Doctorals - Departament - Genètica

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