Periodic repression of Notch pathway genes governs the segmentation of Xenopus embryos.
During the development of the vertebrate embryo, genes encoding components of the Notch signaling pathway are required for subdividing the paraxial mesoderm into repeating segmental structures, called somites. These genes are thought to act in the presomitic mesoderm when cells form prospective somites, called somitomeres, but their exact function remains unknown. To address this issue, we have identified two novel genes, called ESR-4 and ESR-5, which are transcriptionally activated in the somitomeres of Xenopus embryos by the Su(H)-dependent Notch signaling pathway. We show that the expression of these genes divides each somitomere into an anterior and posterior half, and that this pattern of expression is generated by a mechanism that actively represses the expression of the Notch pathway genes when paraxial cells enter a critical region and form a somitomere. Repression of Notch signaling during somitomere formation requires a negative feedback loop and inhibiting the activity of genes in this loop has a profound effect on somitomere size. Finally we present evidence that once somitomeres form, ESR-5 mediates a positive feedback loop, which maintains the expression of Notch pathway genes. We propose a model in which Notch signaling plays a key role in both establishing and maintaining segmental identity during somitomere formation in Xenopus embryos.
Jen
W C
WC
The Salk Institute for Biological Studies, San Diego, California 92186, USA.
Gawantka
V
V
Pollet
N
N
Niehrs
C
C
Kintner
C
C
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D006655:Histone Deacetylases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm; D008969:Molecular Sequence Data; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014981:Xenopus; D029867:Xenopus Proteins
D051792:Basic Helix-Loop-Helix Proteins; D003513:Cycloheximide; D018076:DNA, Complementary; D029721:Drosophila Proteins; D006655:Histone Deacetylases; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D051880:Receptors, Notch; D012097:Repressor Proteins; D029867:Xenopus Proteins; C120192:ESR-5 protein, Xenopus; C088731:Su(H) protein, Drosophila; C120191:hes7.2 protein, Xenopus