Analysis Tools
nervous system
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• at E17.5, the zone of non-proliferation (ZNP) at the apex is widened and encompasses extra hair cells in mutant mice
• proliferating cells are found in the outer sulcus region at E16.5 and inner sulcus region at P0 in the apical turn
• unexpectedly, myosin VIIa immunolabeling revealed ectopic expression in the supporting cell region in both the basal and apical turns of mutant epithelia; these cells probably represent displaced hair cells
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• at P10, homozygotes exhibit a significant increase in cochlear hair cell (HC) number per unit area at the middle and apical regions; however, total hair cell number in the base and middle turns is reduced relative to wild-type mice due to a shorter cochlear duct
• notably, the total number of hair cells is not increased over wild-type, perhaps because of displaced hair cells and a shortened cochlear duct
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• at P10, extra IHCs are typically found in the organ of Corti at the basal and apical region but less frequently in the middle turn
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• at P10, extra OHCs are found in the organ of Corti in the middle-to-apical regions, ranging from one extra row in the middle turn, to three or four extra rows in the apical-most regions
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• at P10, occasional IHCs with stereociliary bundles are displaced from the normal orientation in the organ of Corti
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• at P10, OHC stereociliary bundles are often misoriented
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• at P21, the layer of small granular neurons characteristic of cortical layer IV was missing in mutant mice, primarily due to excessive layer IV cell death; in contrast, cortical layers II/III, V, and VI appeared relatively unaffected
(J:59182)
• although subplate neurons sent projections toward the thalamus, subplate neurons displayed aberrant differentiation and premature cell death during corticogenesis
(J:59182)
• these subplate neuron defects resulted in loss of guidance and innervation of thalamocortical projections, promoting layer IV cell death
(J:59182)
• mutant embryos displayed altered region-specific expression of guidance molecules in the cortex
(J:71195)
• dye-tracing experiments revealed changes in region-specific connections between the cortex and the thalamus, indicating impaired neocortical regionalization in mutant mice
(J:71195)
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• cytochrome oxidase staining of the cortex from the few mutant surviving mice revealed a lack of barrel formation, suggesting impaired ability to perceive sense, vision, and hearing
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hearing/vestibular/ear
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• reduced Notch signaling contributes to increases in support cell differentiation
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• in homozygotes, the sensory epithelium displys extra proliferating cells and ectopic hair cell differentiation in the supporting cell region
• expression analysis of Notch signaling genes revealed attenuated Notch signaling in mutant cochleae, including lack of Jag1 upregulation and Hes5 downregulation in the supporting cells region at E15.5, as well as expansion of the Lfng expression domain to encompass the LER and GER in the early sensory epithelium before hair cells and supporting cells differentiate
• reduced Notch signaling contributes to increases in hair cell and support cell differentiation
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• at E17.5, the zone of non-proliferation (ZNP) at the apex is widened and encompasses extra hair cells in mutant mice
• proliferating cells are found in the outer sulcus region at E16.5 and inner sulcus region at P0 in the apical turn
• unexpectedly, myosin VIIa immunolabeling revealed ectopic expression in the supporting cell region in both the basal and apical turns of mutant epithelia; these cells probably represent displaced hair cells
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• at P10, homozygotes exhibit a significant increase in cochlear hair cell (HC) number per unit area at the middle and apical regions; however, total hair cell number in the base and middle turns is reduced relative to wild-type mice due to a shorter cochlear duct
• notably, the total number of hair cells is not increased over wild-type, perhaps because of displaced hair cells and a shortened cochlear duct
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• at P10, extra IHCs are typically found in the organ of Corti at the basal and apical region but less frequently in the middle turn
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• at P10, extra OHCs are found in the organ of Corti in the middle-to-apical regions, ranging from one extra row in the middle turn, to three or four extra rows in the apical-most regions
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• at P10, occasional IHCs with stereociliary bundles are displaced from the normal orientation in the organ of Corti
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• at P10, OHC stereociliary bundles are often misoriented
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• at P10, homozygotes display supernumerary Deiter's supporting cells beneath each hair cell
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• at E15 and E17, homozygotes exhibit a shorter cochlear duct relative to wild-type mice
• however, no differences in cochlear duct length are noted at E13
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• surviving mutant mice displayed defects in hearing (Fred A. Pereira, unpublished findings)
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cellular
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• reduced Notch signaling contributes to increases in support cell differentiation
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