Completing the set of h/E(spl) cyclic genes in zebrafish: her12 and her15 reveal novel modes of expression and contribute to the segmentation clock

Shankaran, S.S., Sieger, D., Schroter, C., Czepe, C., Pauly, M.C., Laplante, M.A., Becker, T.S., Oates, A.C., and Gajewski, M.
Developmental Biology   304(2): 615-632 (Journal)
Registered Authors
Becker, Thomas S., Gajewski, Martin, Laplante, Mary, Oates, Andrew, Shankaran, Sunita Sathy, Sieger, Dirk
Cyclic h/E(spl) genes, Segmentation clock, Somitogenesis, bHLH transcription factor
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/biosynthesis
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/physiology*
  • Biological Clocks
  • Body Patterning
  • Gene Expression Regulation, Developmental
  • Genome
  • Mesoderm/metabolism
  • Molecular Sequence Data
  • RNA, Messenger/biosynthesis
  • Repressor Proteins/biosynthesis
  • Repressor Proteins/genetics
  • Repressor Proteins/physiology*
  • Zebrafish/embryology
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
17274976 Full text @ Dev. Biol.
Somitogenesis is the key developmental process that lays down the framework for a metameric body in vertebrates. Somites are generated from the un-segmented presomitic mesoderm (PSM) by a pre-patterning process driven by a molecular oscillator termed the segmentation clock. The Delta-Notch intercellular signaling pathway and genes belonging to the hairy (h) and Enhancer of split (E(spl))-related (h/E(spl)) family of transcriptional repressors are conserved components of this oscillator. A subset of these genes, called cyclic genes, is characterized by oscillating mRNA expression that sweeps anteriorly like a wave through the embryonic PSM. Periodic transcriptional repression by H/E(spl) proteins is thought to provide a critical part of a negative feedback loop in the oscillatory process, but it is an open question how many cyclic h/E(spl) genes are involved in the somitogenesis clock in any species, and what distinct roles they might play. From a genome-wide search for h/E(spl) genes in the zebrafish, we previously estimated a total of five cyclic members. Here we report that one of these, the mHes5 homologue her15 actually exists as a very recently duplicated gene pair. We investigate the expression of this gene pair and analyse its regulation and activity in comparison to the paralogous her12 gene, and the other cyclic h/E(spl) genes in the zebrafish. The her15 gene pair and her12 display novel and distinct expression features, including a caudally restricted oscillatory domain and dynamic stripes of expression in the rostral PSM that occur at the future segmental borders. her15 expression stripes demarcate a unique two-segment interval in the rostral PSM. Mutant, morpholino, and inhibitor studies show that her12 and her15 expression in the PSM is regulated by Delta-Notch signaling in a complex manner, and is dependent on her7, but not her1 function. Morpholino-mediated her12 knockdown disrupts cyclic gene expression, indicating that it is a non-redundant core component of the segmentation clock. Over-expression of her12, her15 or her7 disrupts cyclic gene expression and somite border formation, and structure function analysis of Her7 indicates that DNA binding, but not Groucho-recruitment seems to be important in this process. Thus, the zebrafish has five functional cyclic h/E(spl) genes, which are expressed in a distinct spatial configuration. We propose that this creates a segmentation oscillator that varies in biochemical composition depending on position in the PSM.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes