The GTPase Rab8 differentially controls the long- and short-range activity of the Hedgehog morphogen gradient by regulating Hedgehog apico-basal distribution

TY - JOUR

T1 - The GTPase Rab8 differentially controls the long- and short-range activity of the Hedgehog morphogen gradient by regulating Hedgehog apico-basal distribution

AU - Gore, Tanvi

AU - Matusek, Tamás

AU - D'Angelo, Gisela

AU - Giordano, Cécile

AU - Tognacci, Thomas

AU - Lavenant-Staccini, Laurence

AU - Rabouille, Catherine

AU - Thérond, Pascal P

N1 - © 2021. Published by The Company of Biologists Ltd.

PY - 2021/3/9

Y1 - 2021/3/9

N2 - The Hedgehog (Hh) morphogen gradient is required for patterning during metazoan development, yet the mechanisms involved in Hh apical and basolateral release and how this influences short- and long-range target induction are poorly understood. We found that depletion of the GTPase Rab8 in Hh-producing cells induces an imbalance between the level of apically and laterally released Hh. This leads to non-cell-autonomous differential effects on the expression of Hh target genes, namely an increase in its short-range targets and a concomitant decrease in long-range targets. We further found that Rab8 regulates the endocytosis and apico-basal distribution of Ihog, a transmembrane protein known to bind to Hh and to be crucial for establishment of the Hh gradient. Our data provide new insights into morphogen gradient formation, whereby morphogen activity is functionally distributed between apically and basolaterally secreted pools.

AB - The Hedgehog (Hh) morphogen gradient is required for patterning during metazoan development, yet the mechanisms involved in Hh apical and basolateral release and how this influences short- and long-range target induction are poorly understood. We found that depletion of the GTPase Rab8 in Hh-producing cells induces an imbalance between the level of apically and laterally released Hh. This leads to non-cell-autonomous differential effects on the expression of Hh target genes, namely an increase in its short-range targets and a concomitant decrease in long-range targets. We further found that Rab8 regulates the endocytosis and apico-basal distribution of Ihog, a transmembrane protein known to bind to Hh and to be crucial for establishment of the Hh gradient. Our data provide new insights into morphogen gradient formation, whereby morphogen activity is functionally distributed between apically and basolaterally secreted pools.

KW - Animals

KW - Animals, Genetically Modified/metabolism

KW - Drosophila/metabolism

KW - Drosophila Proteins/antagonists & inhibitors

KW - Endocytosis

KW - Endosomes/metabolism

KW - GTP Phosphohydrolases/antagonists & inhibitors

KW - Gene Expression Regulation

KW - Hedgehog Proteins/genetics

KW - Membrane Glycoproteins/genetics

KW - Mutagenesis

KW - Protein Stability

KW - RNA Interference

KW - RNA, Double-Stranded/metabolism

KW - Receptors, Cell Surface/genetics

KW - Signal Transduction

U2 - 10.1242/dev.191791

DO - 10.1242/dev.191791

M3 - Article

C2 - 33547132

SN - 0950-1991

VL - 148

JO - Development (Cambridge)

JF - Development (Cambridge)

IS - 5

ER -