title: SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.
abstract: The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Tony
authors.initials: T
authors.lastname: Oosterveen
authors.forename: Sanja
authors.initials: S
authors.lastname: Kurdija
authors.forename: Mats
authors.initials: M
authors.lastname: Ensterö
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Uhde
authors.forename: Maria
authors.initials: M
authors.lastname: Bergsland
authors.forename: Magnus
authors.initials: M
authors.lastname: Sandberg
authors.forename: Rickard
authors.initials: R
authors.lastname: Sandberg
authors.forename: Jonas
authors.initials: J
authors.lastname: Muhr
authors.forename: Johan
authors.initials: J
authors.lastname: Ericson
mesh_terms: D000818:Animals; D001665:Binding Sites; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002645:Chickens; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics*; D016678:Genome / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism; D018878:Limb Buds / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012176:Retinoids / Q000494:pharmacology; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D012176:Retinoids; D055748:SOXB1 Transcription Factors