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The mechanisms used by embryos to pattern tissues across their axes has fascinated developmental biologists since the founding of embryology. Here, using single-cell technology, we interrogate complex patterning defects and define a Hedgehog (Hh)– fibroblast growth factor (FGF) signaling axis required for anterior mesoderm lineage development during gastrulation. Single-cell transcriptome analysis of Hh-deficient mesoderm revealed selective deficits in anterior mesoderm populations, culminating in defects to anterior embryonic structures, including the pharyngeal arches, heart, and anterior somites. Transcriptional profiling of Hh-deficient mesoderm during gastrulation revealed disruptions to both transcriptional patterning of the mesoderm and FGF signaling for mesoderm migration. Mesoderm-specific Fgf4/Fgf8 double-mutants recapitulated anterior mesoderm defects and Hh-dependent GLI transcription factors modulated enhancers at FGF gene loci. Cellular migration defects during gastrulation induced by Hh pathway antagonism were mitigated by the addition of FGF4 protein. These findings implicate a multicomponent signaling hierarchy activated by Hh ligands from the embryonic node and executed by FGF signals in nascent mesoderm to control anterior mesoderm patterning. [ABSTRACT FROM AUTHOR]

The term 'super-enhancer' has been used to describe groups of putative enhancers in close genomic proximity with unusually high levels of Mediator binding, as measured by chromatin immunoprecipitation and sequencing (ChIP-seq). Here we review the identification and composition of super-enhancers, describe links between super-enhancers, gene regulation and disease, and discuss the functional significance of enhancer clustering. We also provide our perspective regarding the proposition that super-enhancers are a regulatory entity conceptually distinct from what was known before the introduction of the term. Our opinion is that there is not yet strong evidence that super-enhancers are a novel paradigm in gene regulation and that use of the term in this context is not currently justified. However, the term likely identifies strong enhancers that exhibit behaviors consistent with previous models and concepts of transcriptional regulation. In this respect, the super-enhancer definition is useful in identifying regulatory elements likely to control genes important for cell type specification. [ABSTRACT FROM AUTHOR]