Document Detail


Cyclical expression of the Notch/Wnt regulator Nrarp requires modulation by Dll3 in somitogenesis.
MedLine Citation:
PMID:  19268448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Delta-like 3 (Dll3) is a divergent ligand and modulator of the Notch signaling pathway only identified so far in mammals. Null mutations of Dll3 disrupt cycling expression of Notch targets Hes1, Hes5, and Lfng, but not of Hes7. Compared with Dll1 or Notch1, the effects of Dll3 mutations are less severe for gene expression in the presomitic mesoderm, yet severe segmentation phenotypes and vertebral defects result in both human and mouse. Reasoning that Dll3 specifically disrupts key regulators of somite cycling, we carried out functional analysis to identify targets accounting for the segmental phenotype. Using microdissected embryonic tissue from somitic and presomitic mesodermal tissue, we identified new genes enriched in these tissues, including Limch1, Rhpn2, and A130022J15Rik. Surprisingly, we only identified a small number of genes disrupted by the Dll3 mutation. These include Uncx, a somite gene required for rib and vertebral patterning, and Nrarp, a regulator of Notch/Wnt signaling in zebrafish and a cycling gene in mouse. To determine the effects of Dll3 mutation on Nrarp, we characterized the cycling expression of this gene from early (8.5 dpc) to late (10.5 dpc) somitogenesis. Nrarp displays a distinct pattern of cycling phases when compared to Lfng and Axin2 (a Wnt pathway gene) at 9.5 dpc but appears to be in phase with Lfng by 10.5 dpc. Nrarp cycling appears to require Dll3 but not Lfng modulation. In Dll3 null embryos, Nrarp displayed static patterns. However, in Lfng null embryos, Nrarp appeared static at 8.5 dpc but resumed cycling expression by 9.5 and dynamic expression at 10.5 dpc stages. By contrast, in Wnt3a null embryos, Nrarp expression was completely absent in the presomitic mesoderm. Towards identifying the role of Dll3 in regulating somitogenesis, Nrarp emerges as a potentially important regulator that requires Dll3 but not Lfng for normal function.
Authors:
William Sewell; Duncan B Sparrow; Allanceson J Smith; Dorian M Gonzalez; Eric F Rappaport; Sally L Dunwoodie; Kenro Kusumi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-03
Journal Detail:
Title:  Developmental biology     Volume:  329     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-04     Completed Date:  2009-06-04     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  400-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
In Situ Hybridization
Intracellular Signaling Peptides and Proteins / genetics,  physiology*
Membrane Proteins / genetics,  physiology*
Mice
Mice, Mutant Strains
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Proteins / genetics*
Somites / metabolism*
Wnt Proteins / genetics
Wnt3 Protein
Wnt3A Protein
Grant Support
ID/Acronym/Agency:
R01 AR050687/AR/NIAMS NIH HHS; R01 AR050687/AR/NIAMS NIH HHS; R01 AR050687-01/AR/NIAMS NIH HHS; R01 AR050687-02/AR/NIAMS NIH HHS; R01 AR050687-03/AR/NIAMS NIH HHS; R01 AR050687-04/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Dll3 protein, mouse; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Nrarp protein, mouse; 0/Proteins; 0/WNT3A protein, human; 0/Wnt Proteins; 0/Wnt3 Protein; 0/Wnt3A Protein; 0/Wnt3a protein, mouse
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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