CMV-induced embryonic XXXX organ of corti @entity1141 : Network architecture of dysfunctional lateral inhibition.

@entity1 @entity2803 @entity19 @entity2557 @entity1373 @entity600 @entity1274 @entity1141
BACKGROUND: @entity2803 is the major nongenetic cause of @entity1274 at birth and beyond. Among other pathologies, there is a striking @entity1141 / @entity1373 of organ of Corti hair and supporting cells. METHODS: Using an in vitro embryonic @entity19 model of @entity2803 -induced cochlear teratogenesis that mimics the known @entity1 pathology, and functional signaling network modeling, we tested the hypothesis that @entity2803 disrupts the highly ordered organ of Corti hair and supporting cells pattern by dysregulating Notch and @entity2557 , 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   <   1 * 10(-12) ). Furthermore, we determined that the subnetwork has a highly heterogeneous scale-free topology in which the highly linked genes (hubs), Notch and @entity2557 , play a central role in mediating interactions among the less linked genes. CONCLUSION: This phenomenon has important biologic and therapeutic implications. @entity600 Research (Part A) 103:573-582, 2015.    2015 Wiley Periodicals, Inc.
