This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our understanding of the molecular basis of hair cell, sensory neuron and supporting cell development in the ear has seen dramatic progress. However, there is almost no basis for a molecular distinction between vestibular and cochlear histogenesis. Our preliminary data on Lmx1a null (Dreher) mice indicate a dramatic effect on the histogenesis of the basal as compared to the apical half of the organ of Corti: the former assumes a vestibular organ-like histogenesis whereas the latter develops a disturbed but recognizable organ of Corti phenotype. The present application will explore this finding to further our molecular understanding of organ of Corti-specific histogenesis.
In Aim 1 we will characterize the Lmx1a null ear phenotype at the light- and electron microscopic level using in situ hybridization and immunohistochemistry to detect cell specific defects (e.g., SOX2, PROX1).
In Aim 2 we will examine the Lmx1a expression pattern using ISH and expand our understanding of the molecular basis for the null phenotype by comparing the expression of genes generally considered important for cochlear development or uniquely expressed in the cochlea (Gata3, Fgf8, Fgf10). Finally, in Aim 3, we will employ a microarray approach to directly compare gene expression in the apical/basal cochlea and saccule of the Lmx1a null with that in wildtype littermates.
These aims will provide new insight into the molecular basis of the vestibular organ-like phenotype of the basal cochlea of the Lmx1a mutant and, by extension, into the molecular basis of organ of Corti histogenesis. This understanding will be important in attempts to restore the organ of Corti from the flat epithelium of end-stage of cochlear degeneration.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR018788-08
Application #
8360398
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
8
Fiscal Year
2011
Total Cost
$293,016
Indirect Cost
Name
University of Nebraska Medical Center
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Gong, Qiang; Wang, Chao; Zhang, Weiwei et al. (2017) Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data. Sci Rep 7:11301
Goodman, Linda; Zallocchi, Marisa (2017) Integrin ?8 and Pcdh15 act as a complex to regulate cilia biogenesis in sensory cells. J Cell Sci 130:3698-3712
Bouska, A; Zhang, W; Gong, Q et al. (2017) Combined copy number and mutation analysis identifies oncogenic pathways associated with transformation of follicular lymphoma. Leukemia 31:83-91
Donze-Reiner, Teresa; Palmer, Nathan A; Scully, Erin D et al. (2017) Transcriptional analysis of defense mechanisms in upland tetraploid switchgrass to greenbugs. BMC Plant Biol 17:46
Amaradasa, Bimal S; Amundsen, Keenan (2016) Transcriptome Profiling of Buffalograss Challenged with the Leaf Spot Pathogen Curvularia inaequalis. Front Plant Sci 7:715
Gurumurthy, Channabasavaiah B; Grati, M'hamed; Ohtsuka, Masato et al. (2016) CRISPR: a versatile tool for both forward and reverse genetics research. Hum Genet 135:971-6
Rohr, J; Guo, S; Huo, J et al. (2016) Recurrent activating mutations of CD28 in peripheral T-cell lymphomas. Leukemia 30:1062-70
Connor, Alicia L; Kelley, Philip M; Tempero, Richard M (2016) Invariant asymmetry renews the lymphatic vasculature during homeostasis. J Transl Med 14:209
Connor, Alicia L; Kelley, Philip M; Tempero, Richard M (2016) Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis. Lab Invest 96:270-82
Küçük, Can; Hu, Xiaozhou; Gong, Qiang et al. (2016) Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma. Am J Pathol 186:1435-41

Showing the most recent 10 out of 88 publications