1. Hherisomes, Hedgehog specialized recycling endosomes, are required for high level Hedgehog signaling and tissue growth
- Author
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Bram Herpers, Tamás Matusek, Catherine Rabouille, Sandrine Pizette, Pascal P. Thérond, Hubrecht Institute for Developmental Biology and Stem Cell Research, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Center for Molecular medicine [Utrecht], University Medical Center [Utrecht], Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), therond, pascal, Hubrecht Institute [Utrecht, Netherlands], University Medical Center [Utrecht]-Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center Groningen [Groningen] (UMCG), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-15-CE13-0002,HHMOVE,ANALYSE DYNAMIQUE DE L'ACTIVITÉ ORGANISATIONELLE DE HEDGEHOG CHEZ LA DROSOPHILE(2015), ANR-18-CE13-0003,ART-EVs,Identification d'une nouvelle signature protéique de vésicules extracellulaires impliquées dans le développement embryonnaire et pathologie(2018), Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, ANALYSE DYNAMIQUE DE L'ACTIVITÉ ORGANISATIONELLE DE HEDGEHOG CHEZ LA DROSOPHILE - - HHMOVE2015 - ANR-15-CE13-0002 - AAPG2015 - VALID, and APPEL À PROJETS GÉNÉRIQUE 2018 - Identification d'une nouvelle signature protéique de vésicules extracellulaires impliquées dans le développement embryonnaire et pathologie - - ART-EVs2018 - ANR-18-CE13-0003 - AAPG2018 - VALID
- Subjects
Drosophila melanogaster/genetics ,[SDV]Life Sciences [q-bio] ,Endosomes/genetics ,Growth ,0302 clinical medicine ,LONG-RANGE ACTIVITY ,Wings ,Drosophila Proteins ,Wings, Animal ,Small GTPase ,Developmental ,0303 health sciences ,Wing imaginal disc ,Gene Expression Regulation, Developmental ,Hedgehog Proteins/genetics ,Hedgehog signaling pathway ,Endocytosis ,Cell biology ,[SDV] Life Sciences [q-bio] ,Imaginal disc ,Drosophila melanogaster ,Drosophila ,FORM ,Morphogen ,Drosophila Proteins/genetics ,Signal Transduction ,EXPRESSION ,CHOLESTEROL-MODIFIED HEDGEHOG ,Endosome ,Dispatched ,Endosomes ,Biology ,Hherisomes ,03 medical and health sciences ,GRADIENT ,Electron microscopy ,Compartment (development) ,Animals ,Hedgehog Proteins ,TRAFFICKING ,Hedgehog ,COMPARTMENT ,030304 developmental biology ,Animal ,Cell Biology ,Signaling ,Gene Expression Regulation ,Rab11 ,CELLS ,030217 neurology & neurosurgery - Abstract
In metazoans, tissue growth and patterning is partly controlled by the Hedgehog (Hh) morphogen. Using immuno-electron microscopy on Drosophila wing imaginal discs, we identified a cellular structure, the Hherisomes, which contain the majority of intracellular Hh. Hherisomes are recycling tubular endosomes, and their formation is specifically boosted by overexpression of Hh. Expression of Rab11, a small GTPase involved in recycling endosomes, boosts the size of Hherisomes and their Hh concentration. Conversely, increased expression of the transporter Dispatched, a regulator of Hh secretion, leads to their clearance. We show that increasing Hh density in Hherisomes through Rab11 overexpression enhances both the level of Hh signaling and disc pouch growth, whereas Dispatched overexpression decreases high-level Hh signaling and growth. We propose that, upon secretion, a pool of Hh triggers low-level signaling, whereas a second pool of Hh is endocytosed and recycled through Hherisomes to stimulate high-level signaling and disc pouch growth. Altogether, our data indicate that Hherisomes are required to sustain physiological Hh activity necessary for patterning and tissue growth in the wing disc.
- Published
- 2021