The Expression of Messenger RNAs Coding for Growth Factors, Their Receptors, and eph-Class Receptor Tyrosine Kinases in Normal and Ototoxically Damaged Chick Cochleae

Pickles, James O.; Heumen, Walter R.A van

doi:10.1159/000111245

Cited by 41 publications

(52 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Progenitors also continue to divide in serumfree medium, indicating that mitotic substances are intrinsic to the inner ear organs (52,53). A number of fibroblast growth factors that bind and activate tyrosine kinase receptors are known to be present in inner ear organs (54,55). The expression levels of many of these factors are changed after HC damage, although their mitogenic properties have not yet been determined.…”

Section: Mitotic Hc Regenerationmentioning

confidence: 99%

Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

Baird

Burton

Fashena

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Hair cells in many nonmammalian vertebrates are regenerated by the mitotic division of supporting cell progenitors and the differentiation of the resulting progeny into new hair cells and supporting cells. Recent studies have shown that nonmitotic hair cell recovery after aminoglycoside-induced damage can also occur in the vestibular organs. Using hair cell and supporting cell immunocytochemical markers, we have used confocal and electron microscopy to examine the fate of damaged hair cells and the origin of immature hair cells after gentamicin treatment in mitotically blocked cultures of the bullfrog saccule. Extruding and fragmenting hair cells, which undergo apoptotic cell death, are replaced by scar formations. After losing their bundles, sublethally damaged hair cells remain in the sensory epithelium for prolonged periods, acquiring supporting cell-like morphology and immunoreactivity. These modes of damage appear to be mutually exclusive, implying that sublethally damaged hair cells repair their bundles. Transitional cells, coexpressing hair cell and supporting cell markers, are seen near scar formations created by the expansion of neighboring supporting cells. Most of these cells have morphology and immunoreactivity similar to that of sublethally damaged hair cells. Ultrastructural analysis also reveals that most immature hair cells had autophagic vacuoles, implying that they originated from damaged hair cells rather than supporting cells. Some transitional cells are supporting cells participating in scar formations. Supporting cells also decrease in number during hair cell recovery, supporting the conclusion that some supporting cells undergo phenotypic conversion into hair cells without an intervening mitotic event.

show abstract

Section: Mitotic Hc Regenerationmentioning

confidence: 99%

Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

Baird

Burton

Fashena

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…It is generally believed that molecules involved in axon guidance during embryonic development could be reused in the adult after lesioning axon tracts to re-establish the functional integrity of neuronal circuits (Aubert et al 1995). Up-regulation of Eph receptor expression is observed following injury to the adult spinal cord (Miranda et al 1999), hippocampus (Moreno-Flores andWandosell 1999), and cochlear nucleus (Pickles and van Heumen 1997). In lower vertebrates, such as fish and amphibians, retinal ganglion cells (RGCs) are newly formed throughout life, and retinal axons continuously regrow into the tectum.…”

Section: Neuroregenerationmentioning

confidence: 99%

Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function

Palmer¹,

Klein²

2003

Genes Dev.

250

182

View full text Add to dashboard Cite

Cell-to-cell communication during development and plasticity is controlled to a large extent by signaling events downstream of receptor tyrosine kinases (RTKs). Most RTKs bind soluble ligands, which are often produced at a distance from the RTK-expressing cells, and therefore these interactions typically mediate long-range communication. Eph receptors (or Ephs), instead, bind membrane-bound ephrin ligands expressed by neighboring cells and mediate short-range cell-to-cell communication. The influence of ephrin-Eph interaction on cell behavior depends on the cell type, but can in most cases be interpreted as repulsion of neighboring cells or of cellular processes, such as the neuronal growth cone. However, in some cases ephrin-Eph activation can have the opposite effect, that is, increased adhesion/attraction. One subclass of ephrins, the ephrinB ligands, are transmembrane proteins with intrinsic (so-called reverse) signaling properties (for review, see Kullander and Klein 2002). This complicates the interpretation of functional assays and genetic phenotypes, because manipulations intended to eliminate forward receptor function often have consequences for reverse signaling as well. This review summarizes the diverse biological roles of ephrins and Ephs in embryonic development, including patterning and morphogenetic processes of the nervous and vascular systems, and in the adult, such as synaptic plasticity. We further touch upon more recent observations on ephrin functions in neurogenesis, nervous system regeneration, and tumorigenesis. Our focus is on, but is not restricted to, recent findings using genetically amenable systems. General features of ephrins and EphsDuring embryonic and postnatal development, cells need to respond to a changing environment, for example, the release of growth factors and morphogens, the migration of neighboring cells, and the production of extracellular matrix proteins by differentiating cells. Through binding to their cognate protein ligands, receptor tyrosine kinases are sensors of such environmental changes and transmit information to the inside of the cell. Of all the RTKs in the human genome, Eph receptors constitute the largest subfamily, which probably arose through rather recent gene duplications. Its 13 members (in mammals) are subdivided based on sequence similarity and ligand-binding characteristics into an A-subclass (EphA1-EphA8) and a B-subclass (EphB1-EphB4, EphB6) with partially overlapping functions (for reviews, see Wilkinson 2001;Kullander and Klein 2002). Their ligands, the ephrins, are also subdivided into an A-subclass (ephrinA1-ephrinA5), which are tethered to the exoplasmic leaflet of the cell membrane by a glycosylphosphatidylinositol (GPI) anchor, and the B-subclass (ephrinB1-ephrinB3), which contain transmembrane and cytoplasmic regions. EphrinA ligands typically bind to EphA receptors, and ephrinB ligands bind to EphB receptors. The EphA4 receptor has a broader ligand-binding spectrum, as it can bind most ephrinA, as well as ephrinB2 and ephrinB3, but n...

show abstract

“…These growth factors bind to and activate tyrosine kinase receptors, many of which also are expressed in the avian inner ear. PCR studies have shown that mRNAs for FGF receptor (FGFR)-1, epidermal growth factor receptor (erbB1), and IGF receptor-1 are present in the cochlear duct (61) and, more specifically, in the sensory epithelium (59). Further, in situ hybridization reveals abundant message for FGFR-3 in the supporting cells (unpublished observation).…”

Section: Avian Hair Cell Progenitors: Identity and Behaviormentioning

confidence: 89%

“…Further, in situ hybridization reveals abundant message for FGFR-3 in the supporting cells (unpublished observation). After hair cell damage, there are detectable changes in the levels of transcripts for FGF-1, IGF receptor-1, FGFR-1, and FGFR-3, but not for IGF-1, FGF-2, or ErbB1 (59,61). At the protein level, FGFR-1 is present in hair cells in control tissue, and then it becomes elevated in supporting cells after hair cell damage (59,61).…”

Section: Avian Hair Cell Progenitors: Identity and Behaviormentioning

confidence: 99%

“…After hair cell damage, there are detectable changes in the levels of transcripts for FGF-1, IGF receptor-1, FGFR-1, and FGFR-3, but not for IGF-1, FGF-2, or ErbB1 (59,61). At the protein level, FGFR-1 is present in hair cells in control tissue, and then it becomes elevated in supporting cells after hair cell damage (59,61). However, the actual mitogenic properties of most of these growth factors in auditory hair cell regeneration have not yet been determined.…”

Section: Avian Hair Cell Progenitors: Identity and Behaviormentioning

confidence: 99%

See 1 more Smart Citation

Cellular studies of auditory hair cell regeneration in birds

Stone

Rubel

2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A decade ago it was discovered that mature birds are able to regenerate hair cells, the receptors for auditory perception. This surprising finding generated hope in the field of auditory neuroscience that new hair cells someday may be coaxed to form in another class of warm-blooded vertebrates, mammals. We have made considerable progress toward understanding some cellular and molecular events that lead to hair cell regeneration in birds. This review discusses our current understanding of avian hair cell regeneration, with some comparisons to other vertebrate classes and other regenerative systems.

show abstract

The Expression of Messenger RNAs Coding for Growth Factors, Their Receptors, and eph-Class Receptor Tyrosine Kinases in Normal and Ototoxically Damaged Chick Cochleae

Cited by 41 publications

References 27 publications

Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function

Cellular studies of auditory hair cell regeneration in birds

Contact Info

Product

Resources

About