Lateral interactions account for the pattern of the hair cell array in the chick basilar papilla

It has been suggested that lateral interactions set up the array of hair cells and supporting cells in the chick basilar papilla. The presence of a hair cell would inhibit adjacent cells from becoming hair cells, and promote the formation of supporting cells. Models of cell specification were tested, starting with a closely packed array of multipotent progenitor cells. Lateral interactions, in which emerging hair cells promoted a supporting cell phenotype in adjacent cells, and in which emerging supporting cells promoted a hair cell phenotype in adjacent cells, produced an array of cells similar to that observed experimentally in the distal and central parts of the basilar papilla. In these areas, the ratio of supporting cells to hair cells is very close to 2:1, each hair cell on average being surrounded by six supporting cells, and each supporting cell being surrounded by three hair cells and three supporting cells. Identical patterns of hair and supporting cells could be produced by models in which either of the lateral inhibitory factors was replaced by a diffusive factor, i.e. a factor which acts on all cells in the model irrespective of position. The agreement of the model with observed cell ratios supports the view that the fate of both hair cells and supporting cells in the chick basilar papilla is a product of cell interactions within the papilla. It is possible that one factor, that provides contact lateral inhibition and promotes the formation of supporting cells, is the Notch/Delta system. It is possible that the other factor is retinoic acid, a diffusive factor that promotes the formation of hair cells. (C) 2000 Elsevier Science B.V. All rights reserved

The expression of messenger RNAs coding for growth factors, their receptors, and eph-class receptor tyrosine kinases in normal and ototoxically damaged chick cochleae

Messenger RNAs coding for growth factors and receptor tyrosine kinases were measured by quantitative competitive and by semi-quantitative reverse-transcription polymerase chain reaction in whole and dissected chick inner ears. The fibroblast growth factor (FGF) receptor 1 chick embryonic kinase (CEK) 1 was expressed in all structures examined (otocyst, hatchling whole cochlea, cochlear nerve ganglion, and cochlear and vestibular sensory epithelia), although slightly more heavily in the otocyst. The related fibroblast growth factor receptors CEK 2 and 3 were preferentially expressed in the nerve ganglion and in the vestibular sensory epithelium, respectively. FGF 1 mRNA was low in early development, increasing to mature levels at around embryonic age 11 days, while FGF2, mRNA was expressed at constant levels at all ages. In response to ototoxic damage, FGF1 mRNA levels were increased in the early damaged cochlear sensory epithelium. Immunohistochemistry for CEK1 showed that normal hair cells expressed the receptor heavily on the hair cell stereocilia, while with early damage, CEK1 came to be expressed heavily on the apical surfaces of the supporting cells. In normal chicks, the CEK4 and CEK8 eph-class receptor tyrosine kinases were expressed relatively heavily by the cochlear nerve ganglion, and CEK10 was expressed relatively heavily by the cochlear hair cell sensory epithelium. The results suggest that the FGF system may be involved in the response of the cochlear epithelium to ototoxic damage. The eph-class receptor tyrosine kinase CEK10 may be involved in cell interactions in the cochlear sensory epithelium, while CEK4 and CEK8 may play a role in the cochlear innervation

Expression of EphA4 in developing inner ears of the mouse and guinea pig

The expression of EphA4, an Eph-class receptor tyrosine kinase, was determined by immunohistochemistry in developing inner ears of the mouse and the guinea pig. In the mouse, EphA4 expression was visible in the fibroblasts of the spiral ligament and in the structures that were to become the osseous spiral lamina. Cochlear nerve ganglion cells expressed ephrin-B2, and the modiolus expressed mRNA coding for ephrin-B3, both transmembrane ligands for EphA4. In contrast, in the guinea pig, cells of the cochlear nerve ganglion expressed EphA4, as did supporting cells of the organ of Corti (Wensen's cells and inner pillar cells). There was also some expression in fibroblasts of the spiral ligament but none in the structures that were to become the osseous spiral lamina. It is suggested that in the mouse, EphA4 may help direct the cochlear innervation towards the organ of Corti by a repulsive interaction, but that this is highly species dependent. (C) 2000 Elsevier Science B.V. All rights reserved

Fibroblast growth factor receptor-4 splice variants cause deletion of a critical tyrosine

We have identified two novel isoforms of fibroblast growth factor receptor-4 (FGFR4). They result from alternative splicing of intron 17. Two transcripts, both slightly larger than the one coding for the known mouse FGFR4, are generated. The shortest (FGFR4-17a) includes the 31-most 3'-nucleotides of intron 17; the longest (FGFR4-17b) includes all 114 nucleotides of intron 17, Translation of the FGFR4-17a and FGFR4-17b splice variants predicts that both novel putative FGFR4 isoforms have a truncated C-terminal intracellular tail. The first amino acid residue affected by the insertions in both novel isoforms is Tyr-760, a residue that may play a crucial role in intracellular signaling through stimulation of the phosphatidylinositol-biphosphate pathway