Language

English

Publication Date

3-31-2026

Journal

Nature Communications

DOI

10.1038/s41467-026-70804-6

PMID

41917030

PMCID

PMC13199485

PubMedCentral® Posted Date

3-31-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Convergence and extension (C&E) cell movements that elongate the primary embryonic axis are precisely timed during vertebrate gastrulation, but mechanisms controlling their onset remain unknown. Using zebrafish embryonic explants that recapitulate C&E and its timing, we identified sulfatase modifying factor 2 (sumf2) as a candidate trigger gene for C&E onset. sumf2 and its paralog sumf1 encode negative and positive sulfatase regulators, respectively, whose expression levels invert and increase heparan sulfate sulfation during gastrulation. Overexpressing sumf1 or sumf2 causes delayed or precocious C&E, respectively, whereas their loss shifts C&E timing in the opposite direction. We identified Sulf1, a modifier of heparan sulfate proteoglycans (HSPGs), as their key downstream effector and found that altering heparan sulfate sulfation levels shifts C&E onset and suppresses sumf1 and sumf2 mutant phenotypes. This work supports a model in which sumf2 expression reduces sulfatase activity, rewriting HSPG sulfation patterns to promote the onset of C&E morphogenesis.

Keywords

Animals, Zebrafish, Sulfatases, Zebrafish Proteins, Gene Expression Regulation, Developmental, Heparan Sulfate Proteoglycans, Morphogenesis, Sulfotransferases, Gastrulation, Embryo, Nonmammalian, Heparan Sulfate, Gastrulation, Glycobiology, Post-translational modifications

Published Open-Access

yes

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