Pax3 lineage contribution to the mammalian inner and middle ear
포유동물의 내이와 중이 발생에 기여하는 Pax3의 lineage분석
Dept. of Medical Science/석사
The vertebrate inner ear develops from a specialized region of the ectoderm located on either side of the caudal hindbrain known as the otic placode. During development, the otic placode invaginates to form the otic cup, from which some cells delaminate and migrate into neighboring mesenchyme to form neurons of the cochlear-vestibular ganglion. The otic cup deepens further and pinches off from the ectoderm to form the otocyst that will develop into the membranous labyrinth of the inner ear. While a majority of the cells in the membranous labyrinth are derived from the otic placode, some of the cells in the labyrinth are derived from the neural crest. Similarly, the middle ear ossicles, whose role is to relay and to amplify the environmental sound to the inner ear, are also known to be derived from the neural crest. Neural crest cell are originated from the junction between the epidermis and dorsal region of the neural tube and give rise to a variety of cell types such as neurons, glia, melanocytes, bones and cartilages. To better understand the role of neural crest in inner and middle ear development, I genetically fate-mapped the progenies of neural crest using Cre/loxP system. Pax3 is a member of the Pax family of transcription factors and is known to be important for various aspects of embryogenesis including neural crest differentiation. In human, mutations in PAX3 cause Waardenburg''s syndrome Type I, characterized by neurosensory hearing loss. Pax3 is expressed in the dorsal neural tube, from which the neural crest cells are migrated, but not in the developing inner and middle ears. By crossing Pax3-Cre mice with R26R reporter mice, I genetically labeled the cells expressing Pax3 in the dorsal neural tube and identified their descendants during inner and middle ear development using β-galactosidase (β-gal) staining. At E15.5, β-gal positive cells are detected in various substructures of the inner ear including endolymphatic duct, common cruz, semicircular canal, utricle, saccule, vestibular dark cells, stria vascularis, and ganglia. In addition, β-gal positive cells are present in some parts of the otic capsule and in all three middle ear ossicles. Furthermore, analyses of Pax3-Cre homozygous mutant embryos showed that Pax3 is required for melanocytes differentiation of the stria vascularis in the cochlear lateral wall but not for other neural crest-derived cell types in the inner and middle ears.