Proneural gene requirement for hair cell differentiation in the zebrafish lateral line (original) (raw)
Related papers
Regulation of Latent Sensory Hair Cell Precursors by Glia in the Zebrafish Lateral Line
Neuron, 2005
Structure odes, distinct ectodermal thickenings in the head that University of Washington generate specific sensory structures (Stone, 1922; Seattle, Washington 98195 Northcutt et al., 1994; Piotrowski and Northcutt, 1996; 3 National Institutes of Health Raible and Kruse, 2000). In zebrafish, the pLL placode NICHD polarizes at about 20 hr postfertilization (hpf), so that LMG anterior cells will differentiate into neurons, while poste-Bethesda, Maryland 20892 rior cells cluster together to form the 1Њ neuromast pri-4 Department of Neurobiology and Anatomy mordium (primI). PrimI migrates into the trunk along the University of Utah horizontal myoseptum, the midline of the somites (Met-Salt Lake City, Utah 84132 calfe et al., 1985; Kimmel et al., 1995). Periodically, clusters of approximately 25 cells bud off the trailing edge of primI to form a neuromast (Gompel et al., 2001a). The Summary primordium completes its migration by about 42 hpf (Metcalfe et al., 1985; Kimmel et al. , 1995). By 3 days The lateral line is a placodally derived mechanosenpostfertilization (dpf), the complete pattern of 1Њ neurosory organ in anamniotes that detects the movement masts is visible: five or six neuromasts along each side of water. In zebrafish embryos, a migrating primorof the body at intervals of approximately five to seven dium deposits seven to nine clusters of sensory hair somites, plus an additional cluster of two to three neuro-
BMC Developmental Biology, 2009
Background The lateral line system in zebrafish is composed of a series of organs called neuromasts, which are distributed over the body surface. Neuromasts contain clusters of hair cells, surrounded by accessory cells. Results In this report we describe zebrafish prox1 mRNA expression in the migrating primordium and in the neuromasts of the posterior lateral line. Furthermore, using an antibody against Prox1 we characterize expression of the protein in different cell types within neuromasts, and we show distribution among the supporting cells and hair cells. Conclusion Functional analysis using antisense morpholinos indicates that prox1 activity is crucial for the hair cells to differentiate properly and acquire functionality, while having no role in development of other cell types in neuromasts.
Afferent Neurons of the Zebrafish Lateral Line Are Strict Selectors of Hair-Cell Orientation
PLoS ONE, 2009
Hair cells in the inner ear display a characteristic polarization of their apical stereocilia across the plane of the sensory epithelium. This planar orientation allows coherent transduction of mechanical stimuli because the axis of morphological polarity of the stereocilia corresponds to the direction of excitability of the hair cells. Neuromasts of the lateral line in fishes and amphibians form two intermingled populations of hair cells oriented at 180u relative to each other, however, creating a stimulus-polarity ambiguity. Therefore, it is unknown how these animals resolve the vectorial component of a mechanical stimulus. Using genetic mosaics and live imaging in transgenic zebrafish to visualize hair cells and neurons at single-cell resolution, we show that lateralline afferents can recognize the planar polarization of hair cells. Each neuron forms synapses with hair cells of identical orientation to divide the neuromast into functional planar-polarity compartments. We also show that afferent neurons are strict selectors of polarity that can re-establish synapses with identically oriented targets during hair-cell regeneration. Our results provide the anatomical bases for the physiological models of signal-polarity resolution by the lateral line.
Phoenix Is Required for Mechanosensory Hair Cell Regeneration in the Zebrafish Lateral Line
PLoS Genetics, 2009
In humans, the absence or irreversible loss of hair cells, the sensory mechanoreceptors in the cochlea, accounts for a large majority of acquired and congenital hearing disorders. In the auditory and vestibular neuroepithelia of the inner ear, hair cells are accompanied by another cell type called supporting cells. This second cell population has been described as having stem cell-like properties, allowing efficient hair cell replacement during embryonic and larval/fetal development of all vertebrates. However, mammals lose their regenerative capacity in most inner ear neuroepithelia in postnatal life. Remarkably, reptiles, birds, amphibians, and fish are different in that they can regenerate hair cells throughout their lifespan. The lateral line in amphibians and in fish is an additional sensory organ, which is used to detect water movements and is comprised of neuroepithelial patches, called neuromasts. These are similar in ultra-structure to the inner ear's neuroepithelia and they share the expression of various molecular markers. We examined the regeneration process in hair cells of the lateral line of zebrafish larvae carrying a retroviral integration in a previously uncharacterized gene, phoenix (pho). Phoenix mutant larvae develop normally and display a morphologically intact lateral line. However, after ablation of hair cells with copper or neomycin, their regeneration in pho mutants is severely impaired. We show that proliferation in the supporting cells is strongly decreased after damage to hair cells and correlates with the reduction of newly formed hair cells in the regenerating phoenix mutant neuromasts. The retroviral integration linked to the phenotype is in a novel gene with no known homologs showing high expression in neuromast supporting cells. Whereas its role during early development of the lateral line remains to be addressed, in later larval stages phoenix defines a new class of proteins implicated in hair cell regeneration.
Proceedings of the National Academy of Sciences, 2014
Significance Hearing impairment is most frequently caused by the loss of sensory hair cells in the cochlea. One potential means of alleviating hearing loss is to restore these cells, which do not naturally regenerate in mammals. The zebrafish lateral line serves as a useful model for studying hair-cell regeneration because in this system there exist progenitors, mantle cells, from which hair-cell precursors originate. We have produced zebrafish with fluorescently labeled mantle cells, isolated those cells by flow cytometry, and analyzed the transcripts that they express. We have also defined the temporal window during which mantle cells respond to hair-cell death. This approach has identified genes representing unexpected signaling pathways that may contribute to the development of treatments for hearing loss.
Mechanisms of Development, 2001
Expression of a mouse atonal homologue, math1, de®nes cells with the potential to become sensory hair cells in the mouse inner ear (Science 284 (1999) 1837) and Notch signaling limits the number of cells that are permitted to adopt this fate (Nat. Genet. 21 (1999) 289; J. Neurocytol. 28 (1999) 809). Failure of lateral inhibition mediated by Notch signaling is associated with an overproduction of ear hair cells in the zebra®sh mind bomb (mib) and deltaA mutants (Development 125 (1998a) 4637; Development 126 (1999) 5669), suggesting a similar role for these genes in limiting the number of hair cells in the zebra®sh ear. This study extends the analysis of proneural and neurogenic gene expression to the lateral line system, which detects movement via clusters of related sensory hair cells in specialized structures called neuromasts. We have compared the expression of a zebra®sh atonal homologue, zath1, and neurogenic genes, deltaA, deltaB and notch3, in neuromasts and the posterior lateral line primordium (PLLP) of wild-type and mib mutant embryos. We describe progressive restriction of proneural and neurogenic gene expression in the migrating PLLP that appears to correlate with selection of hair cell fate in maturing neuromasts. In mib mutants there is a failure to restrict expression of zath1 and Delta homologues in the neuromasts revealing similarities with the phenotype previously described in the ear.
Synaptically silent sensory hair cells in zebrafish are recruited after damage
Nature Communications, 2018
Analysis of mechanotransduction among ensembles of sensory hair cells in vivo is challenging in many species. To overcome this challenge, we used optical indicators to investigate mechanotransduction among collections of hair cells in intact zebrafish. Our imaging reveals a previously undiscovered disconnect between hair-cell mechanosensation and synaptic transmission. We show that saturating mechanical stimuli able to open mechanically gated channels are unexpectedly insufficient to evoke vesicle fusion in the majority of hair cells. Although synaptically silent, latent hair cells can be rapidly recruited after damage, demonstrating that they are synaptically competent. Therefore synaptically silent hair cells may be an important reserve that acts to maintain sensory function. Our results demonstrate a previously unidentified level of complexity in sculpting sensory transmission from the periphery.
Kinocilia Mediate Mechanosensitivity in Developing Zebrafish Hair Cells
Developmental Cell, 2012
Mechanosensitive cilia are vital to signaling and development across many species. In sensory hair cells, sound and movement are transduced by apical hair bundles. Each bundle is comprised of a single primary cilium (kinocilium) flanked by multiple rows of actin-filled projections (stereocilia). Extracellular tip links that interconnect stereocilia are thought to gate mechanosensitive channels. In contrast to stereocilia, kinocilia are not critical for hair-cell mechanotransduction. However, by sequentially imaging the structure of hair bundles and mechanosensitivity of individual lateral-line hair cells in vivo, we uncovered a central role for kinocilia in mechanosensation during development. Our data demonstrate that nascent hair cells require kinocilia and kinocilial links for mechanosensitivity. Although nascent hair bundles have correct planar polarity, the polarity of their responses to mechanical stimuli is initially reversed. Later in development, a switch to correctly polarized mechanosensitivity coincides with the formation of tip links and the onset of tip-link-dependent mechanotransduction.
Development Genes and Evolution, 2001
A number of genes that are involved in somitogenesis in vertebrates are cyclically expressed in the presomitic mesoderm. These include homologues of the Drosophila genes fringe and hairy. We have analysed here two genes that belong to these classes in the zebrafish, namely the apparent orthologues of lunatic fringe (l-fng) and of c-hairy1 (called her9). However, unlike the respective mouse and chicken genes, they are not expressed cyclically in the presomitic mesoderm. Instead, both genes are mainly expressed in the central nervous system. her9 is predominantly expressed in the fore- and midbrain, and transiently in the hindbrain. Thus, the previously identified and only very distantly related her1 gene of zebrafish has more similarities to the expression of the c-hairy1 gene than its apparent orthologue her9, indicating that sequence similarity and similarity of function are not necessarily linked in this case. l-fng expression is found in alternating pre-rhombomeres, comparable to the equivalent mouse gene expression and in the anterior compartments of the mature somites, which was also shown for the chicken l-fng gene. The latter expression indicates that it might be involved in boundary definition and cell fate decision processes, rather than in pre-patterning of the somites. Interestingly, a similar role has previously been inferred for the grasshopper homologue of l-fng. This suggests that the function of l-fng in boundary definition of the somites might be ancestral, while its recruitment to the pre-patterning process of the somites might be a derived feature in higher vertebrates.
Coordinate development of skin cells and cutaneous sensory axons in zebrafish
The Journal of Comparative Neurology, 2012
Peripheral sensory axons innervate the epidermis early in embryogenesis to detect touch stimuli. To characterize the time course of cutaneous innervation and the nature of interactions between sensory axons and skin cells at early developmental stages, we conducted a detailed analysis of cutaneous innervation in the head, trunk and tail of zebrafish embryos and larvae from 18 to 78 hours post-fertilization. This analysis combined live imaging of fish expressing transgenes that highlight sensory neurons and skin cells, ...