title: 2- and 6-O-sulfated proteoglycans have distinct and complementary roles in cranial axon guidance and motor neuron migration.
abstract: The correct migration and axon extension of neurons in the developing nervous system is essential for the appropriate wiring and function of neural networks. Here, we report that O-sulfotransferases, a class of enzymes that modify heparan sulfate proteoglycans (HSPGs), are essential to regulate neuronal migration and axon development. We show that the 6-O-sulfotransferases HS6ST1 and HS6ST2 are essential for cranial axon patterning, whilst the 2-O-sulfotransferase HS2ST (also known as HS2ST1) is important to regulate the migration of facial branchiomotor (FBM) neurons in the hindbrain. We have also investigated how HS2ST interacts with other signals in the hindbrain and show that fibroblast growth factor (FGF) signalling regulates FBM neuron migration in an HS2ST-dependent manner.
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Miguel
authors.identifier: 0000-0002-2024-1499
authors.initials: M
authors.lastname: Tillo
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Camille
authors.identifier: 0000-0003-1904-4612
authors.initials: C
authors.lastname: Charoy
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Quenten
authors.identifier: 0000-0002-5958-4181
authors.initials: Q
authors.lastname: Schwarz
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Maden
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Davidson
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fantin
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK Yale Cardiovascular Research Centre, Yale University, New Haven, CT 06511, USA c.ruhrberg@ucl.ac.uk.
authors.forename: Christiana
authors.identifier: 0000-0002-3212-9381
authors.initials: C
authors.lastname: Ruhrberg
mesh_terms: D000818:Animals; D000071437:Axon Guidance / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D012886:Skull / Q000187:drug effects / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D011509:Proteoglycans; D013431:Sulfates; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D015238:Sulfotransferases
keywords: Axon guidance; Fibroblast growth factor (FGF); Heparan sulfate proteoglycan (HSPG); Neuron migration; Sulfotransferase; Vascular endothelial growth factor (VEGF)