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High-probability grants
According to our matching algorithm, Martin L. Basch is the likely recipient of the following grants.
| Years |
Recipients |
Code |
Title / Keywords |
Matching
score |
| 2017 — 2021 |
Basch, Martin L |
R01Activity Code Description:
To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Role of Endothelin Signaling in the Development of Intermediate Cells in the Stria Vascularis @ Case Western Reserve University
ABSTRACT The stria vascularis is a specialized epithelial structure of the mammalian cochlea that produces endolymph, the potassium-rich fluid responsible for the positive endocochlear potential of the cochlear lumen. This positive extracellular potential is the major driving force for proper signal transduction by sensory cells in the ear, and thus normal hearing. The stria vascularis is the ?battery? of the auditory organ. It is localized in the lateral wall of the cochlea, and consists of a multilayered highly vascularized epithelium. It is composed of three main cell types with distinct embryonic origins: the marginal cells derived from the otic epithelium, the intermediate cells which are specialized melanocyte-like cells derived from migratory neural crest cells, and the basal cells that are derived from otic mesenchyme. Mesoderm-derived blood vessels are interspersed between these cells throughout the stria. Defects in the development of the stria vascularis are part of a number of inheritable deafness syndromes in humans, including Hirschsprung disease and Waardenburg, Jervell and Lange-Nielsen, Bartter and SeSAME syndromes. Over the past decade, a great effort has been made to understand the development of the sensory cells in the mammalian cochlea with the aim of applying their developmental principles to regenerative therapies. By contrast, very little is known about the developmental potential of the stria vascularis, or even the mechanisms of strial degeneration due to aging. Our long-term goal is to understand the principles that govern the development of the stria and apply them to devise reparative and regenerative therapies for cases of congenital strial defects or strial presbycusis. Neural crest cells are a transient population of multipotent migratory embryonic cells. In the inner ear, neural crest cells give rise to the glia of the VIIIth ganglion and the intermediate cells of the stria vascularis. Intermediate cells are necessary for normal strial function and although they seem to share a common origin with melanoblasts, melanin itself is not necessary for hearing. Mutations that affect neural crest development or migration often result in syndromes that include deafness. Mutations of the human endothelin receptor B gene (Ednrb) result in Hirschsprung's disease. The sensorineural deafness in this syndrome is a consequence of the atrophied stria vascularis that lacks intermediate cells. The goal of this proposal is to investigate the migration, differentiation and interactions of neural crest-derived intermediate cells with other cells in the stria vascularis and the role that Endothelin signaling plays in these processes.
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