CMV-induced embryonic mouse organ of corti dysplasia: Network architecture of dysfunctional lateral inhibition
| Autor: | Michael Melnick, Tina Jaskoll |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Embryology
Pathology medicine.medical_specialty General Medicine Biology Hyperplasia medicine.disease Embryonic stem cell Cell biology medicine.anatomical_structure Lateral inhibition Dysplasia Organ of Corti Pediatrics Perinatology and Child Health Gene expression medicine Sensorineural hearing loss Gene Developmental Biology |
| Zdroj: | Birth Defects Research Part A: Clinical and Molecular Teratology. 103:573-582 |
| ISSN: | 1542-0752 |
| Popis: | Background Congenital cytomegalovirus infection is the major nongenetic cause of sensorineural hearing loss at birth and beyond. Among other pathologies, there is a striking dysplasia/hyperplasia of organ of Corti hair and supporting cells. Methods Using an in vitro embryonic mouse model of cytomegalovirus-induced cochlear teratogenesis that mimics the known human pathology, and functional signaling network modeling, we tested the hypothesis that cytomegalovirus disrupts the highly ordered organ of Corti hair and supporting cells pattern by dysregulating Notch and Fgfr3, their cognate ligands and downstream effectors. Results Several novel emergent properties of the critical lateral inhibition subnetwork became apparent. The subnetwork has classic small-world properties such as short paths between most gene pairs, few long-distance links, and considerable clustering. Concomitantly, the calculated probability that our specific gene expression dataset is from dysplastic organs of Corti is highly significant (p |
| Databáze: | OpenAIRE |
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