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| Status |
Public on Jan 16, 2023 |
| Title |
Zebrafish her3 knockout impacts developmental and cancer-related gene signatures |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
HES3 is a basic helix-loop-helix transcription factor that regulates neural stem cell renewal during development. HES3 overexpression is predictive of reduced overall survival in patients with fusion-positive rhabdomyosarcoma, a pediatric cancer that resembles immature and undifferentiated skeletal muscle. However, the mechanisms of HES3 cooperation in fusion-positive rhabdomyosarcoma are unclear and are likely related to her3/HES3’s role in neurogenesis. To further investigate how HES3 functions during development, we generated a zebrafish CRISPR/Cas9 knockout of her3, the zebrafish ortholog of HES3. Zebrafish her3 mutants are not embryonic lethal and as adults exhibit expected Mendelian ratios. Embryonic her3 zebrafish mutants are significantly smaller than wildtype and present with lens defects as adults. Transcriptomic analysis of her3 mutant embryos indicates that genes involved in organ development, such as pctp and grinab, are significantly downregulated. Further, differentially expressed genes in her3 knockout embryos are enriched for HOX and sox10 motifs. Several cancer-related gene pathways are impacted, including the inhibition of matrix metalloproteinases. Altogether, this new model is a powerful system to study her3/HES3-mediated neural development and its misappropriation in cancer contexts.
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| Overall design |
6 different conditions were analyzed, each with 3 biological replicates, from zebrafish (Danio rerio). Each sample was a pool of 20-25 embryos at either 24 hour post-fertilization (hpf) or 72hpf. Wildtype WIK zebrafish were used as a control at both 24hpf and 72hpf. Wildtype WIK embryos were used for the her3-morpholino (MO) and mismatch(mm)-MO injections. Morpholino injections were only analyzed at 24hpf. mm-MO injected samples were used as an additional control for her3-MO injected samples. her3-knockout (her3_38aa samples) were analyzed at both 24hpf and 72hpf.
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| Contributor(s) |
Kent MR, Calderon D, Silvius KM, Kucinski JP, LaVigne CA, Cannon MV, Kendall GC |
| Citation(s) |
36696714 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 CA272872 |
Understanding Infantile Rhabdomyosarcoma Biology and Therapeutic Targets |
The Research Institute at Nationwide Children's Hospital |
Genevieve Claire Kendall |
|
| Submission date |
Feb 15, 2022 |
| Last update date |
Feb 20, 2023 |
| Contact name |
Genevieve Kendall |
| E-mail(s) |
Genevieve.Kendall@NationwideChildrens.org
|
| Phone |
6143552928
|
| Organization name |
Nationwide Children's Hospital / The Ohio State University
|
| Lab |
Kendall Lab
|
| Street address |
700 Children's Drive, WA5014
|
| City |
Columbus |
| State/province |
OH |
| ZIP/Postal code |
43205 |
| Country |
USA |
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| Platforms (1) |
| GPL24995 |
Illumina NovaSeq 6000 (Danio rerio) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA807347 |
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