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bioRxivJan 2025 DOI:
10.1101/2025.10.09.681375

Sulfatase modifying factors control the timing of zebrafish gastrulation morphogenesis

Cervino, AS; Basu, A; Weiss, RJ; Kaur Bajwa, G
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Abstract
To shape the emerging body plan, morphogenetic cell movements must be coordinated not only in space, 16 but also in time. Convergence and Extension (C&E) movements that elongate the anteroposterior axis initiate 17 with precise timing during vertebrate gastrulation, but the mechanisms controlling their onset remain unknown. 18 We examined this question using zebrafish embryonic explants that faithfully recapitulate C&E cell movements 19 and their precise timing in culture, in isolation from other gastrulation movements. We determined that new 20 transcription is required at gastrulation onset for C&E in explants and identified sulfatase modifying factor 2 21 (sumf2) as a candidate ‘trigger’ gene expressed at this time. sumf2 and its paralog sumf1 encode negative and 22 positive regulators, respectively, of all sulfatase enzymes, which remove sulfate groups from their substrates, 23 altering their biological activity. In zebrafish embryos and explants, sumf1 and sumf2 expression levels invert at 24 gastrulation onset, predicting a reduction in sulfatase activity and consequent increase of substrate sulfation. 25 We found that overexpressing sumf1 and sumf2 causes delayed or precocious C&E onset, respectively, 26 whereas loss of sumf1 and sumf2 function shifts C&E timing in the opposite direction. We further identified 27 Sulf1, an extracellular sulfatase that modifies heparan sulfate proteoglycans (HSPGs), as the key effector by 28 which sumf1 and sumf2 control C&E timing. Accordingly, reduced or increased levels of sulfated heparan sulfate similarly shift C&E onset and suppress sumf1 and sumf2 mutant phenotypes. Together, our work 30 supports a model in which sumf2 expression at zebrafish gastrulation onset reduces sulfatase activity, rewriting 31 HSPG sulfation patterns to promote and/or permit C&E morphogenesis.
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