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Status |
Public on Mar 11, 2009 |
Title |
MOE430A Analysis of Dll3 mutant vs. wild-type 9.5 dpc presomitic mesoderm |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
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, Rphn2, 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.
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Overall design |
To enrich for genes in the presomitic mesoderm that are specifically disrupted by Dll3 mutation, we compared microdissected tissues from wild-type and Dll3 mutant embryos. We generated biological replicate pools from Dll3+/+ (wild-type) or Dll3neo/neo embryos for a total of six pools. Microarray analysis using Affymetrix MOE430A arrays was carried out on the biological pool triplicates for both wild-type and mutant genotypes.
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Contributor(s) |
Sewell W, Sparrow DB, Smith AJ, Gonzalez DM, Rappaport EF, Dunwoodie SL, Kusumi K |
Citation(s) |
19268448 |
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Submission date |
Mar 08, 2009 |
Last update date |
Jan 08, 2019 |
Contact name |
Kenro Kusumi |
E-mail(s) |
kenro@asu.edu
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Phone |
480-727-8993
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Fax |
480-965-6899
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URL |
http://sols.asu.edu/faculty/kkusumi.php
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Organization name |
Arizona State University
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Department |
School of Life Sciences
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Street address |
PO Box 874501
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City |
Tempe |
State/province |
AZ |
ZIP/Postal code |
85287 |
Country |
USA |
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Platforms (1) |
GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE15178 |
Presomitic mesoderm and somite-level tissue of 9.5 dpc Dll3 mutants |
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Relations |
BioProject |
PRJNA123113 |
Supplementary file |
Size |
Download |
File type/resource |
GSE15152_RAW.tar |
53.8 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
Processed data included within Sample table |
Processed data provided as supplementary file |
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