Hair Cells and Supporting Cells Share a Common Progenitor in the Avian Inner Ear

Abstract

Sensory organs of the vertebrate inner ear contain two major cell types: hair cells (HCs) and supporting cells (SCs). To study the lineage relationships between these two populations, replication-defective retroviral vectors encoding marker genes were delivered to the otic vesicle of the chicken embryo. The resulting labeled clones were analyzed in the hearing organ of the chicken, called the basilar papilla (BP), after cellular differentiation. BPs were allowed to develop for 2 weeks after delivery of the retrovirus, were removed, and were processed histochemically as whole mounts to identify clones of cells. Clusters of labeled cells were evident in the sensory epithelium, the nonsensory epithelium, and in adjacent tissues. Labeled cell types included HCs, two morphologically distinct types of SCs, homogene cells, border cells, hyaline cells, ganglion cells, and connective tissue cells. Each clone was sectioned and cell-type identification was performed on sensory clones expressing retrovirally transduced ␤-galactosidase. Cell composition was determined for 41 sensory clones, most of which contained both HCs and SCs. Clones containing one HC and one SC were observed, suggesting that a common progenitor exists that can remain bipotential up to its final mitotic division. The possibility that these two cell types may also arise from a mitotic precursor during HC regeneration in the mature basilar papilla is consistent with their developmental history.

Mutant mice reveal the molecular and cellular basis for specific sensory connections to inner ear epithelia and primary nuclei of the brain

“…The importance of the delta-notch system mediated upregulation of bHLH genes in the CNS development has recently been established through mutational analysis (Hatakeyama et al, 2004). Since hair cell and supporting cell formation is clonally linked (Fekete et al, 1998) and hair cells are involved in the regulation of supporting cell maturation through the delta-notch system (Zine et al, 2001), elimination of hair cell precursors might result in abrogation of entire sensory epithelia. It is, therefore, possible that elimination of the entire formation of sensory patches may be required to investigate the role of other guiding mechanisms to bring fibers to specific sensory epithelia.…”

“…However, it cannot be ruled out that other factors generated by supporting cells contribute to the apparent attraction generated by hair cells. This is so because hair cells and supporting cells are clonally related and always occur together in a normal ear (Fekete et al, 1998). Also, supporting cells express the neurotrophin Ntf3 (Farinas et al, 2001;Pirvola et al, 1992).…”

Somatic transgenesis using retroviral vectors in the chicken embryo

“…RDlac1 virus (and presumably CHAP virus) can infect early chick blastoderm (Reddy et al, 1991). Coinjection of RDlac1 and CHAP (or CHAPOL; see below) viruses has been used to assess clonal boundaries in lineage analysis in the cerebellum , retina (Fekete et al, 1994), and inner ear (Fekete et al, 1998;Lang and Fekete, 2001). …”

Molecular characterization of conditionally immortalized cell lines derived from mouse early embryonic inner ear

“…We hypothesized that this finding could result from differential phenotype development in different cells within single cultures and, thus, designed the immunocytochemical experiments to test this hypothesis. HCs and SCs in vivo are known to originate from a common precursor (Fekete et al, 1998). The alternate hypothesis was that gene expression would be uniform from cell to cell within each cell line.…”