TY - JOUR
T1 - Hherisomes, Hedgehog specialized recycling endosomes, are required for high level Hedgehog signaling and tissue growth
AU - Pizette, Sandrine
AU - Matusek, Tamás
AU - Herpers, Bram
AU - Thérond, Pascal P
AU - Rabouille, Catherine
N1 - © 2021. Published by The Company of Biologists Ltd.
PY - 2021/5/15
Y1 - 2021/5/15
N2 - 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.
AB - 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.
KW - Animals
KW - Drosophila Proteins/genetics
KW - Drosophila melanogaster/genetics
KW - Endosomes/genetics
KW - Gene Expression Regulation, Developmental
KW - Hedgehog Proteins/genetics
KW - Signal Transduction
KW - Wings, Animal
U2 - 10.1242/jcs.258603
DO - 10.1242/jcs.258603
M3 - Article
C2 - 34028543
SN - 0021-9533
VL - 134
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 10
ER -