ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Heparan sulfotransferases Hs6st1 and Hs2st keep Erk in check for mouse corpus callosum development.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Transcription factor 4 regulates the interhemispheric midline remodeling through neuron-astroglia communications during corpus callosum formation.Translational psychiatry · 2025Article
- Article
- Identifying foetal forebrain interneurons as a target for monogenic autism risk factors and the polygenic 16p11.2 microdeletion.BMC neuroscience · 2023Article
- CaCell death & disease · 2022Article
- Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation.International journal of molecular sciences · 2022Review
- Bi-allelic Pathogenic Variants in HS2ST1 Cause a Syndrome Characterized by Developmental Delay and Corpus Callosum, Skeletal, and Renal Abnormalities.American journal of human genetics · 2020Article
- Mutations in SMARCB1 and in other Coffin-Siris syndrome genes lead to various brain midline defects.Nature communications · 2019Article
- Heparan Sulfate Sulfation by Hs2st Restricts Astroglial Precursor Somal Translocation in Developing Mouse Forebrain by a Non-Cell-Autonomous Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- New tools for carbohydrate sulfation analysis: heparan sulfate 2-The Biochemical journal · 2018Article
- Deciphering functional glycosaminoglycan motifs in development.Current opinion in structural biology · 2018Review
- Wnt Signalling Drives Context-Dependent Differentiation or Proliferation in Neuroblastoma.Neoplasia (New York, N.Y.) · 2018Article
- Regulation of eosinophil recruitment and allergic airway inflammation by heparan sulfate proteoglycan (HSPG) modifying enzymes.Experimental lung research · 2018Article
- Flexible Roles for Proteoglycan Sulfation and Receptor Signaling.Trends in neurosciences · 2018Review
- Diverse roles for glycosaminoglycans in neural patterning.Developmental dynamics : an official publication of the American Association of Anatomists · 2018Review
- FGF8 morphogen gradients are differentially regulated by heparan sulphotransferases Hs2st and Hs6st1 in the developing brain.Biology open · 2017Article
- Desulfation of Heparan Sulfate by Sulf1 and Sulf2 Is Required for Corticospinal Tract Formation.Scientific reports · 2017Article
- Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers.International journal of molecular sciences · 2017Review
- Panels of chemically-modified heparin polysaccharides and natural heparan sulfate saccharides both exhibit differences in binding to Slit and Robo, as well as variation between protein binding and cellular activity.Molecular bioSystems · 2016Article
- 2- and 6-O-sulfated proteoglycans have distinct and complementary roles in cranial axon guidance and motor neuron migration.Development (Cambridge, England) · 2016Article
- The role of heparan sulphate in development: the ectodermal story.International journal of experimental pathology · 2016Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The corpus callosum (CC) connects the left and right cerebral hemispheres in mammals and its development requires intercellular communication at the telencephalic midline mediated by signaling proteins. Heparan sulfate (HS) is a sulfated polysaccharide that decorates cell surface and extracellular matrix proteins and regulates the biological activity of numerous signaling proteins via sugar-protein interactions. HS is subject to regulated enzymatic sulfation and desulfation and an attractive, although not proven, hypothesis is that the biological activity of HS is regulated by a sugar sulfate code. Mutant mouse embryos lacking the heparan sulfotransferases Hs2st or Hs6st1 have severe CC phenotypes and form Probst bundles of noncrossing axons flanking large tangles of midline glial processes. Here, we identify a precocious accumulation of Sox9-expressing glial cells in the indusium griseum region and a corresponding depletion at the glial wedge associated with the formation of Probst bundles along the rostrocaudal axis in both mutants. Molecularly, we found a surprising hyperactivation of Erk signaling in Hs2st(-/-) (2-fold) and Hs6st1(-/-) (6-fold) embryonic telencephalon that was most striking at the midline, where Erk signaling is lowest in wild-types, and a 2-fold increase in Fgf8 protein levels in Hs6st1(-/-) embryos that could underpin Erk hyperactivation and excessive glial movement to the indusium griseum. The tightly linked Hs6st1(-/-) CC glial and axonal phenotypes can be rescued by genetic or pharmacological suppression of Fgf8/Erk axis components. Overall, our data fit a model in which Hs2st and Hs6st1 normally generate conditions conducive to CC development by generating an HS-containing environment that keeps Erk signaling in check.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.