Referencia

PLoSBiol 10(4): e1001298. doi:10.1371/journal.pbio.1001298

Autores

Patricia Rojas Ríos, Isabel Guerrero Vega y Acaimo González Reyes.

Resumen

Stem cells reside in specialised microenvironments, or niches, which often contain support cells that control stem cell maintenance and proliferation. Hedgehog (Hh) proteins mediate homeostasis in several adult niches, but a detailed understanding of Hh signalling in stem cell regulation is lacking. Studying the Drosophila female germline stem cell (GSC) niche, we show that Hh acts as a critical juxtacrine signal to maintain the normal GSC population of the ovary. Hh production in cap cells, a type of niche support cells, is regulated by the Engrailed transcription factor. Hh is then secreted to a second, adjacent population of niche cells, the escort cells, where it activates transcription of the GSC essential factors Decapentaplegic (Dpp) and Glass bottom boat (Gbb). In wild-type niches, Hh protein decorates short filopodia that originate in the support cap cells and that are functionally relevant, as they are required to transduce the Hh pathway in the escort cells and to maintain a normal population of GSCs. These filopodia, reminiscent of wing disc cytonemes, grow several fold in length if Hh signalling is impaired within the niche. Because these long cytonemes project directionally towards the signalling-deficient region, cap cells sense and react to the strength of Hh pathway transduction in the niche. Thus, the GSC niche responds to insufficient Hh signalling by increasing the range of Hh spreading. Although the signal(s) perceived by the cap cells and the receptor(s) involved are still unknown, our results emphasise the integration of signals necessary to maintain a functional niche and the plasticity of cellular niches to respond to challenging physiological conditions.

Descripción

Este trabajo describe el papel de diferentes moléculas de señalización en el nicho de las células troncales de la línea germinal (GSCs, del inglés Germline Stem Cells) de Drosophila melanogaster. La ruta de señalización de Hedgehog (Hh), regulada por la acción de Engrailed, induce la expresión de dos proteínas de secreción, Dpp y Gbb, en el nicho de las GSCs. En colaboración con la Dra. Isabel Guerrero Vega (CBM), se ha caracterizado el transporte de Hh en el nicho de las GSCs. La difusión de Hh está mediada por proyecciones celulares denominadas citonemas en el nicho de las GSCs. Las células del nicho reponden a cambios en la señalización de Hh proyectando citonemas de mayor longitud indicando que el nicho posee cierta plasticidad frente a cambios en las condiciones fisiológicas.

imagen abril

REFERENCIA DEL GRUPO INVESTIGADOR

El objetivo principal del grupo del Dr. Acaimo González Reyes en el Centro Andaluz de Biología del Desarrollo (CABD) es la identificación y caracterización de los mecanismos moleculares responsables del mantenimiento, proliferación y diferenciación de las células troncales adultas. Para llevar a cabo estos estudios, se emplea como modelo experimental las células troncales de la línea germinal de la hembra de Drosophilamelanogaster.

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