# Hemocyte-secreted papilin bearing mucin-type O-glycans regulates peripodial stalk formation via epidermal JAK/STAT signaling in Drosophila

## TL;DR

This study shows how a protein modified with sugars in fruit fly blood cells helps control leg development by regulating signaling in nearby tissues.

## Contribution

The paper identifies a novel glycan-mediated signaling mechanism involving hemocyte-secreted Papilin in Drosophila leg morphogenesis.

## Key findings

- Loss of dC1GalT1 causes mispositioned leg discs due to failed stalk formation.
- Hemocyte-derived T antigen suppresses epidermal JAK/STAT signaling to regulate leg development.
- Papilin carrying T antigen is secreted by blood cells to drive stalk tubulogenesis.

## Abstract

Protein glycosylation is an essential post-translational modification. In evolutionarily conserved mucin-type O-glycosylation, the most common O-glycan, T antigen, is synthesized by core 1 β1,3-galactosyltransferase 1 (C1GalT1). Loss of C1GalT1 leads to developmental defects across organisms. We previously found that Drosophila C1GalT1 mutants exhibit malformed legs, but the underlying mechanism was unclear. Here, we identify a glycan-mediated inter-tissue signaling mechanism wherein embryonic hemocytes regulate leg morphogenesis. We show that T antigen-modified Papilin (Ppn), an extracellular matrix (ECM) protein secreted by embryonic hemocytes, suppresses JAK/STAT signaling in the epidermis surrounding Keilin’s organ. This repression is essential for proper tubulogenesis of the peripodial stalk anchoring the leg disc and ensuring its correct positioning during development. Disrupted mucin-type O-glycosylation impairs Ppn secretion and causes mislocalized leg discs and morphogenetic defects. These findings identify Ppn carrying mucin-type O-glycan as long-range modulators of epithelial signaling and underscore the role of immune-like cells in coordinating organogenesis via ECM.

•Loss of dC1GalT1 leads to mispositioned leg discs due to the failure of stalk formation•Embryonic hemocyte-derived T antigen suppresses the epidermal JAK/STAT pathway•Papilin is a candidate core-protein carrying T antigen in hemocytes•Blood cell-secreted Papilin drives stalk tubulogenesis

Loss of dC1GalT1 leads to mispositioned leg discs due to the failure of stalk formation

Embryonic hemocyte-derived T antigen suppresses the epidermal JAK/STAT pathway

Papilin is a candidate core-protein carrying T antigen in hemocytes

Blood cell-secreted Papilin drives stalk tubulogenesis

Biochemistry; Glycobiology; Cell biology; Developmental biology