Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors.
Vertebrate somitogenesis comprises the generation of a temporal periodicity, the establishment of anteroposterior compartment identity, and the translation of the temporal periodicity into the metameric pattern of somites. Molecular players at each of these steps are beginning to be identified. Especially, members of the Notch signaling cascade appear to be involved in setting up the somitogenesis clock and subsequent events. We had previously demonstrated specific expression of the mHey1 and mHey2 basic helix-loop-helix (bHLH) factors during somitogenesis. Here we show that perturbed Notch signaling in Dll1 and Notch1 knockout mutants affects this expression in the presomitic mesoderm (PSM) and the somites. In the caudal PSM, however, mHey2 expression is maintained and thus is likely to be independent of Notch signaling. Furthermore, we analysed the dynamic expression of the respective chicken c-Hey1 and c-Hey2 genes during somitogenesis. Not only is c-Hey2 rhythmically expressed across the chicken presomitic mesoderm like c-hairy1, but its transcription is similarly independent of de novo protein synthesis. In contrast, the dynamic expression of c-Hey1 is restricted to the anterior segmental plate. Both c-Hey genes are coexpressed with c-hairy1 in the posterior somite half. Further in vitro and in vivo interaction assays demonstrated direct homo- and heterodimerisation between these hairy-related bHLH proteins, suggesting a combinatorial action in both the generation of a temporal periodicity and the anterior-posterior somite compartmentalisation.
Leimeister
C
C
Institute of Physiological Chemistry I, Theodor-Boveri-Institute (Biocenter), University of Wuerzburg, Am Hubland, Wuerzburg, D-97074, Germany.
Dale
K
K
Fischer
A
A
Klamt
B
B
Hrabe de Angelis
M
M
Radtke
F
F
McGrew
M J
MJ
Pourquié
O
O
Gessler
M
M
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000502:physiology*; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009024:Morphogenesis; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D019170:Somites / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D014157:Transcription Factors; C405694:Hairy, HRT1 protein; C497762:Notch1 protein, mouse; C064045:delta protein; C109424:hairy1 protein, Gallus gallus