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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 02, 2022 |
| Title |
Identification of in vivo roles of ErbB4-JMa and its direct nuclear signaling using a novel isoform-specific knock out mouse |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Like all receptor tyrosine kinases (RTKs), ErbB4 signals through a canonical signaling involving phosphorylation cascades. However, ErbB4 can also signal through a non-canonical mechanism whereby the intracellular domain is released into the cytoplasm by regulated intermembrane proteolysis (RIP) and translocates to the nucleus where it regulates transcription. These different signaling mechanisms depend on the generation of alternative spliced isoforms, a RIP cleavable ErbB4-JMa and an uncleavable ErbB4-JMb. Non-canonical signaling by ErbB4-JMa has been implicated in the regulation of brain, heart, mammary gland, lung, and immune cell development. However, most studies on non-canonical ErbB4 signaling have been performed in vitro due to the lack of an adequate mouse model. We created an ErbB4-JMa specific knock out mouse and demonstrate that RIP-dependent, non-canonical signaling by ErbB4-JMa is required for the regulation of GFAP expression during cortical development. We also show that ErbB4-JMa signaling is not required for the development of the heart, mammary glands, sensory ganglia. Furthermore, we identify genes whose expression during cortical development is regulated by ErbB4, and show that the expression of two of them, CRYM and DBi, depend on ErbB4-JMa. Thus, we provide the first animal model to study the roles of non-canonical RTK in vivo.
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| Overall design |
mRNA profiles of wild-type (WT) and ErbB4 KO E15.5 cortex (n = 4 of each genotype)
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| Contributor(s) |
Doherty R, MacLeod BL, Nelson MM, Ibrahim MM, Borges BC, Jaradat NW, Finneran MC, Giger RJ, Corfas G |
| Citation(s) |
36241655 |
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| Submission date |
May 02, 2022 |
| Last update date |
Oct 31, 2022 |
| Contact name |
Gabriel Corfas |
| E-mail(s) |
corfas@med.umich.edu
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| Organization name |
University of Michgian
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| Department |
Otolaryngology
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| Street address |
1150 West Medical Center Dr.
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| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109-5616 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA834110 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE202063_DEseq2_with_mm9.txt.gz |
621.6 Kb |
(ftp)(http) |
TXT |
| GSE202063_RAW.tar |
810.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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