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.
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Data availability
Raw RNA-sequencing data were previously published71 and are available in NCBI Gene Expression Omnibus under accession number GSE246158. Raw data for LC-MS analysis of glycosaminoglycans generated in this study are available at GlycoPOST144 under project ID GPST000676. All image and gene expression analysis data generated for this study are available in the Supplementary and Source Data files. Source data are provided with this paper.
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Acknowledgements
We thank Dr. Lila Solnica-Krezel for sharing plasmids and WISH probes, the BCM Center for Comparative Medicine for taking excellent care of our fish, and the Zebrafish International Resource Center for preserving and distributing fish lines used here and by countless members of the community. Thanks also to all members of the Williams lab for their help and feedback on this project, and to Drs. Maria Cecilia Cirio and Lance Davidson for their thoughtful comments on the manuscript. This work was supported by NIH/NICHD grants R00HD091386 and R01HD104784 to M.K.W. The glycosaminoglycan disaccharide analyses were supported by NIH grant R35GM150736 to R.J.W., and those performed at the CCRC were partially supported by NIH grant R24GM137782 to Parastoo Azadi. G.K.B. was supported by a Bourses d’excellence (Université de Montréal) and a FRQ Doctoral Scholarship. CIHR grants (PJT-178037, PJT-204048) and FRQS J1 and J2 awards provided support for R.M.J. S.G. and C.C. were partially supported by CPRIT RP210227 and RP200504, NIH/NCI P30 shared resource grant CA125123, NIH/NIEHS P42 ES027725 and P30 ES030285. Data analysis was performed on the HPC cluster that is managed by the Biostatistics and Informatics Shared Resource (BISR) and supported by an NIH S10 Shared Instrument Grant S10-OD032185, NCI P30-CA125123 and Institutional funds from the Dan L Duncan Comprehensive Cancer Center and Baylor College of Medicine.
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A.S.C. and M.K.W. conceived of the project. A.S.C. and M.K.W. performed zebrafish experiments, R.J.W. and A.B. performed HS disaccharide profiling, and R.M.J. and G.K.B. generated the sulf1 deletion line. S.G. and C.C. performed bioinformatic analysis. A.S.C and M.K.W. wrote the original manuscript. All authors reviewed the manuscript.
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Cervino, A.S., Basu, A., Weiss, R.J. et al. Sulfatase modifying factors control the timing of zebrafish convergence and extension morphogenesis. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70804-6
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DOI: https://doi.org/10.1038/s41467-026-70804-6
