title: Dynamics of sonic hedgehog signaling in the ventral spinal cord are controlled by intrinsic changes in source cells requiring sulfatase 1.
abstract: In the ventral spinal cord, generation of neuronal and glial cell subtypes is controlled by Sonic hedgehog (Shh). This morphogen contributes to cell diversity by regulating spatial and temporal sequences of gene expression during development. Here, we report that establishing Shh source cells is not sufficient to induce the high-threshold response required to specify sequential generation of ventral interneurons and oligodendroglial cells at the right time and place in zebrafish. Instead, we show that Shh-producing cells must repeatedly upregulate the secreted enzyme Sulfatase1 (Sulf1) at two critical time points of development to reach their full inductive capacity. We provide evidence that Sulf1 triggers Shh signaling activity to establish and, later on, modify the spatial arrangement of gene expression in ventral neural progenitors. We further present arguments in favor of Sulf1 controlling Shh temporal activity by stimulating production of active forms of Shh from its source. Our work, by pointing out the key role of Sulf1 in regulating Shh-dependent neural cell diversity, highlights a novel level of regulation, which involves temporal evolution of Shh source properties.
authors.affiliation: University of Toulouse, Center for Developmental Biology, UMR 5547 CNRS, 118 Route de Narbonne, 31062 Toulouse, France.
authors.forename: Amir
authors.initials: A
authors.lastname: Al Oustah
authors.forename: Cathy
authors.initials: C
authors.lastname: Danesin
authors.forename: Nagham
authors.initials: N
authors.lastname: Khouri-Farah
authors.forename: Marie-Amélie
authors.initials: MA
authors.lastname: Farreny
authors.forename: Nathalie
authors.initials: N
authors.lastname: Escalas
authors.forename: Philippe
authors.initials: P
authors.lastname: Cochard
authors.forename: Bruno
authors.initials: B
authors.lastname: Glise
authors.forename: Cathy
authors.initials: C
authors.lastname: Soula
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D053823:Hedgehog Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000145:classification / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013429:Sulfatases / Q000235:genetics / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; C524053:Shha protein, zebrafish; D029961:Zebrafish Proteins; C486773:Sulf1 protein, mouse; D015238:Sulfotransferases; C582441:Sulf1 protein, zebrafish; D013429:Sulfatases
keywords: Floor plate; Neural cell fate; Shh; Spinal cord; Sulfatase1; Zebrafish