Genetic manipulation of the germline stem cell niche in Drosophila ovaries reveals that support cells ensure the maintenance of stem cells by modulating the spread of Hedgehog within the niche

A Callejo

A Forbes

A. J Zhu

A. P McMahon

Acaimo González-Reyes

B. A Chase

C Dahmann

C Eugster

C Nüsslein-Volhard

C Torroja

D Kirilly

D. T Scadden

E Decotto

E Gustavson

E Traiffort

E. J Ward

F King

F-A Ramirez-Weber

G Struhl

Isabel Guerrero

J Bolívar

J Jiang

J Krzemien

J Pearson

J. D Lee

J. E Hooper

J. J Lee

J. S Doctor

K Amanai

K Somogyi

K. A Wharton

K. J Livak

L Lopez-Onieva

L Mandal

L Wang

L. X Morris

M Liu

M van den Heuvel

M Varjosalo

N. M Sherer

Patricia Rojas-Ríos

R Burke

S Bogdan

S Brabletz

S Mendez-Ferrer

S Roy

S Takashima

S. J Morrison

S. L Crittenden

T Xie

Thomas Kornberg

W Tworzydlo

X Song

English

PubMed

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

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PLoS Biology

Cytoneme-mediated delivery of hedgehog regulates the expression of bone morphogenetic proteins to maintain germline stem cells in Drosophila.

<div><p>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 <em>Drosophila</em> 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.</p> </div

Patricia Rojas-Ríos (173846)

Isabel Guerrero (173850)

Acaimo González-Reyes (173855)

The Francis Crick Institute

Cytoneme-Mediated Delivery of Hedgehog Regulates the Expression of Bone Morphogenetic Proteins to Maintain Germline Stem Cells in <em>Drosophila</em>

Resumen del trabajo presentado al XXXIV Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Barcelona del 5 al 8 de septiembre del 2011.Peer reviewe

Rojas-Ríos, Patricia

Guerrero Vega, Isabel

González-Reyes, Acaimo

Digital.CSIC

Señalización celular y desarrollo   Cytoneme-mediated delivery of Hedgehog regulates the expression of bone morphogenetic proteins to maintain germline stem cells in Drosophila  Patricia  Rojas Ríos1, Isabel Guerrero2 y Acaimo González-Reyes1  1 Centro Andaluz de Biología del Desarrollo (CSIC-UPO), Sevilla,  2 Centro de Biología Molecular “Severo Ochoa”. CSIC-UAM, Madrid  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 and Hh is secreted to a second, adjacent population of niche cells, the escort stem cells, where it activates transcription of the GSC essential factors Dpp and 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 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, support 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. 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. 

Cytoneme-mediated delivery of Hedgehog regulates the expression of bone morphogenetic proteins to maintain germline stem cells in Drosophila

Crossref

Cytoneme-Mediated Delivery of Hedgehog Regulates the Expression of Bone Morphogenetic Proteins to Maintain Germline Stem Cells in Drosophila

This is an open-access article distributed under the terms of the Creative Commons Attribution License.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. © 2012 Rojas-Ríos et al.This work was supported by the Spanish Ministerio de Ciencia e Innovación and the FEDER programme (grants BFU2006-10934 and BFU2009-08013 to A.G.-R. and BFU2005-04183 and BFU2008-03320 to I. G., and the CONSOLIDER programme CSD-2007-00008), the EU (Marie Curie RTN FP6 (RTN 035528-2) and FP7 (ITN 238186) to I. G.) and by the Junta de Andalucía (Proyectos de Excelencia P06-CVI-01592 and P09-CVI-5058 to A.G.-R.). P.R.-R. was funded by an I3P-CSIC studentship and by the CONSOLIDER programme.Peer Reviewe

Rojas-Ríos Patricia

Guerrero Isabel

González-Reyes Acaimo

Public Library of Science (PLOS)

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https://figshare.com/articles/Cytoneme_Mediated_Delivery_of_Hedgehog_Regulates_the_Expression_of_Bone_Morphogenetic_Proteins_to_Maintain_Germline_Stem_Cells_in_Drosophila_/126859

Cytoneme-Mediated Delivery of Hedgehog Regulates the Expression of Bone Morphogenetic Proteins to Maintain Germline Stem Cells in Drosophila

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