Combined HS6ST1 and HS6ST2 loss disrupts the formation and migration of gonadotropin-releasing hormone neurons.
Overview
- University of Milan, Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Via Balzaretti 9, 20133 Milan, Italy
- UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Abstract
6-O sulfotransferase (HS6ST) enzymes modify heparan sulphate proteoglycans (HSPGs) to promote growth factor binding to extracellular matrix or receptors. HS6ST1 variants are reported in individuals with GnRH deficiency (GD), which is caused by the defective development of gonadotropin releasing hormone (GnRH) neurons. However, it is unknown whether and how HS6ST family members cooperate in GnRH neuron development. Here, we show that Hs6st1 and Hs6st2 are co-expressed in the mouse nasal neurogenic epithelia, where GnRH neurons and their migratory substrate, the terminal nerve, originate. The combined but not individual disruption of Hs6st1 and Hs6st2 disrupted vomeronasal organ formation with incomplete penetrance, and impaired brain entry of GnRH neurons, similar to observations in mice with loss of the morphogen FGF8 or the axon guidance cue SEMA3A, respectively. In agreement with a role for HS6ST-modified HSPG in regulating SEMA3A signalling, SEMA3A binding to nasal tissues was impaired in the absence of HS6ST1 and HS6ST2. Our results establish a mechanistic role for HS6ST1 in GD and suggest HS6ST2 as an additional susceptibility locus for GD.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE234871, at NCBI GEO; found in the text, “Hs6st1 and Hs6st2 are co-expressed during GnRH…”
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 2, 28 September 2026
- Publisher: n/a → The Company of Biologists
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 5 keywords, 16 MeSH terms, 6 funders, 40 references.
Cite
This paper
Oleari, R., Amoruso, F., Lettieri, A., Ioannou, E., Paganoni, A. J. J., Gimmelli, J., Campinoti, S., Manzini, S., Ruhrberg, C., & Cariboni, A. (2026). Combined HS6ST1 and HS6ST2 loss disrupts the formation and migration of gonadotropin-releasing hormone neurons. Development (Cambridge, England), 153(16), dev204788. https://
BibTeX
@article{oleari2026combi
author = {Oleari, Roberto and Amoruso, Federica and Lettieri, Antonella and Ioannou, Elena and Paganoni, Alyssa J. J. and Gimmelli, Jessica and Campinoti, Sara and Manzini, Stefano and Ruhrberg, Christiana and Cariboni, Anna},
title = {{Combined HS6ST1 and HS6ST2 loss disrupts the formation and migration of gonadotropin-releasing hormone neurons}},
journal = {Development (Cambridge, England)},
year = {2026},
month = jul,
volume = {153},
number = {16},
pages = {dev204788},
publisher = {The Company of Biologists},
issn = {0950-1991},
doi = {10.1242/
url = {https://
pmid = {42358159},
pmcid = {PMC13480955}
}
RIS
TY - JOUR
AU - Oleari, Roberto
AU - Amoruso, Federica
AU - Lettieri, Antonella
AU - Ioannou, Elena
AU - Paganoni, Alyssa J. J.
AU - Gimmelli, Jessica
AU - Campinoti, Sara
AU - Manzini, Stefano
AU - Ruhrberg, Christiana
AU - Cariboni, Anna
TI - Combined HS6ST1 and HS6ST2 loss disrupts the formation and migration of gonadotropin-releasing hormone neurons
T2 - Development (Cambridge, England)
J2 - Development
PY - 2026
DA - 2026/
VL - 153
IS - 16
SP - dev204788
SN - 0950-1991
PB - The Company of Biologists
DO - 10.1242/
UR - https://
LA - en
ER -
CSL-JSON
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"language": "en",
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