期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 18, 页码 7330-7335出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1220010110
关键词
Sox3; Gli; Sox2; positional information
资金
- Swedish Research Council [33X-06555]
- Royal Swedish Academy of Sciences
- Swedish Foundation for Strategic Research (Center of Excellence in Developmental Biology) [SRL10-0030]
- Knut and Alice Wallenberg Foundation [KAW2011.0161]
- Karolinska Institutet
- Wenner-Gren Foundation
- European Union Marie Curie [MEIF-CT-2006-025416]
- Swedish Foundation for Strategic Research (SSF) [SRL10-0030] Funding Source: Swedish Foundation for Strategic Research (SSF)
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.
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