Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4637-4644 ◽  
Author(s):  
C. Haddon ◽  
Y.J. Jiang ◽  
L. Smithers ◽  
J. Lewis
Keyword(s):  
Cell Differentiation ◽  
Lateral Inhibition ◽  
Hair Cells ◽  
Sensory Cell ◽  
Cell Types ◽  
Notch Signalling ◽  
Supporting Cells ◽  
Fine Grained ◽  
Mechanosensory Hair Cells ◽  
The Mind

Mechanosensory hair cells in the sensory patches of the vertebrate ear are interspersed among supporting cells, forming a fine-grained pattern of alternating cell types. Analogies with Drosophila mechanosensory bristle development suggest that this pattern could be generated through lateral inhibition mediated by Notch signalling. In the zebrafish ear rudiment, homologues of Notch are widely expressed, while the Delta homologues deltaA, deltaB and deltaD, coding for Notch ligands, are expressed in small numbers of cells in regions where hair cells are soon to differentiate. This suggests that the delta-expressing cells are nascent hair cells, in agreement with findings for Delta1 in the chick. According to the lateral inhibition hypothesis, the nascent hair cells, by expressing Delta protein, would inhibit their neighbours from becoming hair cells, forcing them to be supporting cells instead. The zebrafish mind bomb mutant has abnormalities in the central nervous system, somites, and elsewhere, diagnostic of a failure of Delta-Notch signalling: in the CNS, it shows a neurogenic phenotype accompanied by misregulated delta gene expression. Similar misregulation of delta; genes is seen in the ear, along with misregulation of a Serrate homologue, serrateB, coding for an alternative Notch ligand. Most dramatically, the sensory patches in the mind bomb ear consist solely of hair cells, which are produced in great excess and prematurely; at 36 hours post fertilization, there are more than ten times as many as normal, while supporting cells are absent. A twofold increase is seen in the number of otic neurons also. The findings are strong evidence that lateral inhibition mediated by Delta-Notch signalling controls the pattern of sensory cell differentiation in the ear.

Cell fate choices and the expression of Notch, Delta and Serrate homologues in the chick inner ear: parallels with Drosophila sense-organ development

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4645-4654 ◽  
Author(s):  
J. Adam ◽  
A. Myat ◽  
I. Le Roux ◽  
M. Eddison ◽  
D. Henrique ◽  
...  
Keyword(s):  
Inner Ear ◽  
Cell Fate ◽  
Hair Cells ◽  
Early Stage ◽  
Sense Organ ◽  
Cell Types ◽  
Developmental Pathways ◽  
Supporting Cells ◽  
Notch Ligand ◽  
Developmental Program

The sensory patches in the vertebrate inner ear are similar in function to the mechanosensory bristles of a fly, and consist of a similar set of cell types. If they are truly homologous structures, they should also develop by similar mechanisms. We examine the genesis of the neurons, hair cells and supporting cells that form the sensory patches in the inner ear of the chick. These all arise from the otic epithelium, and are produced normally even in otic epithelium cultured in isolation, confirming that their production is governed by mechanisms intrinsic to the epithelium. First, the neuronal sublineage becomes separate from the epithelial: between E2 and E3.5, neuroblasts delaminate from the otocyst. The neuroblasts then give rise to a mixture of neurons and neuroblasts, while the sensory epithelial cells diversify to form a mixture of hair cells and supporting cells. The epithelial patches where this occurs are marked from an early stage by uniform and maintained expression of the Notch ligand Serrate1. The Notch ligand Delta1 is also expressed, but transiently and in scattered cells: it is seen both early, during neuroblast segregation, where it appears to be in the nascent neuroblasts, and again later, in the ganglion and in differentiating sensory patches, where it appears to be in the nascent hair cells, disappearing as they mature. Delta-Notch-mediated lateral inhibition may thus act at each developmental branchpoint to drive neighbouring cells along different developmental pathways. Our findings indicate that the sensory patches of the vertebrate inner ear and the sensory bristles of a fly are generated by minor variations of the same basic developmental program, in which cell diversification driven by Delta-Notch and/or Serrate-Notch signalling plays a central part.

scholarly journals Stiffness and tension gradients of the hair cell’s tip-link complex in the mammalian cochlea

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Mélanie Tobin ◽  
Atitheb Chaiyasitdhi ◽  
Vincent Michel ◽  
Nicolas Michalski ◽  
Pascal Martin
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Frequency Tuning ◽  
Cell Types ◽  
Outer Hair Cells ◽  
Tip Link ◽  
Biophysical Mechanism ◽  
Apical Half ◽  
Mechanosensory Hair Cells ◽  
The Brain

Sound analysis by the cochlea relies on frequency tuning of mechanosensory hair cells along a tonotopic axis. To clarify the underlying biophysical mechanism, we have investigated the micromechanical properties of the hair cell’s mechanoreceptive hair bundle within the apical half of the rat cochlea. We studied both inner and outer hair cells, which send nervous signals to the brain and amplify cochlear vibrations, respectively. We find that tonotopy is associated with gradients of stiffness and resting mechanical tension, with steeper gradients for outer hair cells, emphasizing the division of labor between the two hair-cell types. We demonstrate that tension in the tip links that convey force to the mechano-electrical transduction channels increases at reduced Ca2+. Finally, we reveal gradients in stiffness and tension at the level of a single tip link. We conclude that mechanical gradients of the tip-link complex may help specify the characteristic frequency of the hair cell.

Notch signaling regulates the pattern of auditory hair cell differentiation in mammals

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3373-3383 ◽  
Author(s):  
A. Zine ◽  
T.R. Van De Water ◽  
F. de Ribaupierre
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Notch Signaling ◽  
Cell Fate ◽  
Hair Cells ◽  
Expression Patterns ◽  
Sensory Epithelium ◽  
Supporting Cells ◽  
Hair Cell Differentiation ◽  
Notch1 Signaling Pathway

The development of the mammalian cochlea is an example of patterning in the peripheral nervous system. Sensory hair cells and supporting cells in the cochlea differentiate via regional and cell fate specification. The Notch signaling components shows both distinct and overlapping expression patterns of Notch1 receptor and its ligands Jagged1 (Jag1) and Jagged2 (Jag2) in the developing auditory epithelium of the rat. On embryonic day 16 (E16), many precursor cells within the Kolliker's organ immunostained for the presence of both Notch1 and Jag1, while the area of hair cell precursors did not express either Notch1 and Jag1. During initial events of hair cell differentiation between E18 and birth, Notch1 and Jag1 expression predominated in supporting cells and Jag2 in nascent hair cells. Early after birth, Jag2 expression decreased in hair cells while the pattern of Notch1 expression now included both supporting cells and hair cells. We show that the normal pattern of hair cell differentiation is disrupted by alteration of Notch signaling. A decrease of either Notch1 or Jag1 expression by antisense oligonucleotides in cultures of the developing sensory epithelium resulted in an increase in the number of hair cells. Our data suggest that the Notch1 signaling pathway is involved in a complex interplay between the consequences of different ligand-Notch1 combinations during cochlear morphogenesis and the phases of hair cell differentiation.

scholarly journals Hear, Hear for Notch: Control of Cell Fates in the Inner Ear by Notch Signaling

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 370 ◽  
Author(s):  
Rogers Brown ◽  
Andrew K. Groves
Keyword(s):  
Hair Cell ◽  
Notch Signaling ◽  
Inner Ear ◽  
Hair Cells ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Cell Regeneration ◽  
Hair Cell Regeneration ◽  
Supporting Cells ◽  
Fine Grained

The vertebrate inner ear is responsible for detecting sound, gravity, and head motion. These mechanical forces are detected by mechanosensitive hair cells, arranged in a series of sensory patches in the vestibular and cochlear regions of the ear. Hair cells form synapses with neurons of the VIIIth cranial ganglion, which convey sound and balance information to the brain. They are surrounded by supporting cells, which nourish and protect the hair cells, and which can serve as a source of stem cells to regenerate hair cells after damage in non-mammalian vertebrates. The Notch signaling pathway plays many roles in the development of the inner ear, from the earliest formation of future inner ear ectoderm on the side of the embryonic head, to regulating the production of supporting cells, hair cells, and the neurons that innervate them. Notch signaling is re-deployed in non-mammalian vertebrates during hair cell regeneration, and attempts have been made to manipulate the Notch pathway to promote hair cell regeneration in mammals. In this review, we summarize the different modes of Notch signaling in inner ear development and regeneration, and describe how they interact with other signaling pathways to orchestrate the fine-grained cellular patterns of the ear.

scholarly journals Determination and Commitment of Mechanosensory Hair Cells

2002 ◽  
Vol 2 ◽  
pp. 1079-1094 ◽  
Author(s):  
Matthew W. Kelley
Keyword(s):  
Hair Cell ◽  
Signaling Pathways ◽  
Hair Cells ◽  
Progenitor Cell ◽  
Supporting Cells ◽  
Cell Identity ◽  
Final Choice ◽  
Sensory Epithelia ◽  
Cellular Factors ◽  
Mechanosensory Hair Cells

Sound and movement are perceived through the vibration of modified ciliary bundles located on the apical surfaces of specialized mechanosensory hair cells. These hair cells derive from specific regions of the otocyst that become determined to develop initially as sensory epithelia and ultimately as either hair cells or supporting cells. The number of hair cells in an individual vertebrate is surprisingly small and the ability to replace these cells varies among different classes. The molecular and cellular factors that specify hair cell identity are not known, but the results of recent experiments have begun to identify some of the signaling pathways that play important roles in hair cell development. This review will describe recent findings related to the factors that influence the final choice of a progenitor cell to develop as a hair cell and discuss their implications for the overall development of the auditory and vestibular systems.

Variability of hair cells in the coronal organ of ascidians (Chordata, Tunicata)

2010 ◽  
Vol 88 (6) ◽  
pp. 567-578 ◽  
Author(s):  
Federico Caicci ◽  
Valentina Degasperi ◽  
Fabio Gasparini ◽  
Giovanna Zaniolo ◽  
Marcello Del Favero ◽  
...  
Keyword(s):  
Water Flow ◽  
Hair Cells ◽  
Sensory Cell ◽  
Secretory Activity ◽  
Sensory Cells ◽  
Sensory Organs ◽  
Supporting Cells ◽  
Embryonic Origin

The tunicate ascidians are nonvertebrate chordates that possess mechanoreceptor cells in the coronal organ in the oral siphon, which monitor the incoming water flow. Like vertebrate hair cells, the mechanoreceptor–coronal cells are secondary sensory (axonless) cells accompanied by supporting cells and they exhibit morphological diversities of apical specialisations: they are multiciliate in ascidians of the order Enterogona, whereas they are more complex and possess one or two cilia accompanied by stereovilli, also graded in length, in ascidians of the order Pleurogona. In morphology, embryonic origin, and arrangement, coronal sensory cells closely resemble vertebrate hair cells. We describe here the coronal organs of five ascidians ( Pyura haustor (Stimpson, 1864), Pyura stolonifera (Heller, 1878), Styela gibbsii (Stimpson, 1864), Styela montereyensis (Dall, 1872), and Polyandrocarpa zorritensis (Van Name, 1931)), belonging to Pleurogona, also comprising species of one family (Pyuridae), not yet considered, and thus completing our overview of the order. Each species possesses at least two kinds of secondary sensory cells, some of them characterized by stereovilli graded in length. In some species, the coronal sensory cells exhibit secretory activity; in P. haustor, a mitotic sensory cell has also been found. We compare the coronal organ in both ascidians and with other chordate sensory organs formed of secondary sensory cells, and discuss their possible homologies.

scholarly journals Promotion of In Vitro Hair Cell-like Cell Differentiation from Human Embryonic Stem Cells through the Regulation of Notch Signaling

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 873
Author(s):  
Fengjiao Chen ◽  
Ying Yang ◽  
Jianling Chen ◽  
Zihua Tang ◽  
Qian Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Hair Cell ◽  
Hair Cells ◽  
Embryonic Stem ◽  
Temporal Expression ◽  
Supporting Cells ◽  
Temporal Expression Pattern ◽  
Notch Ligands

The Notch signaling pathway plays an important role in otic neurogenesis by regulating the differentiation of inner ear hair cells and supporting cells. Notch-regulated differentiation is required for the regeneration of hair cells in the inner ear. The temporal expression pattern of Notch ligands and receptors during in vitro hair cell-like cell differentiation from human embryonic stem cells (hESCs) was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Subsequently, pAJ-U6-shRNA-CMV-Puro/GFP recombinant lentiviral vectors encoding short hairpin RNAs were used to silence JAG-1, JAG-2, and DLL-1, according to the temporal expression pattern of Notch ligands. Then, the effect of each ligand on the in vitro differentiation of hair cells was examined by RT-PCR, immunofluorescence, and scanning electron microscopy (SEM). The results showed that the individual deletion of JAG-2 or DLL-1 had no significant effect on the differentiation of hair cell-like cells. However, the simultaneous inhibition of both DLL-1 and JAG-2 increased the number of hair cell-like cells and decreased the number of supporting cells. JAG-2 and DLL-1 may have a synergistic role in in vitro hair cell differentiation.

scholarly journals Sox2 and Sox3 are essential for development and regeneration of the zebrafish lateral line

2019 ◽  
Author(s):  
Cristian A. Undurraga ◽  
Yunzi Gou ◽  
Pablo C. Sandoval ◽  
Viviana A. Nuñez ◽  
Miguel L. Allende ◽  
...  
Keyword(s):  
Stem Cells ◽  
Lateral Line ◽  
Hair Cells ◽  
Topological Analysis ◽  
Time Lapse ◽  
Cell Types ◽  
Lateral Line System ◽  
Loss Of Function ◽  
Supporting Cells ◽  
Line System

ABSTRACTThe recovery of injured or lost sensory neurons after trauma, disease or aging is a major scientific challenge. Upon hearing loss or balance disorder, regeneration of mechanosensory hair cells has been observed in fish, some amphibians and under special circumstances in birds, but is absent in adult mammals. In aquatic vertebrates, hair cells are not only present in the inner ear but also in neuromasts of the lateral line system. The zebrafish lateral line neuromast has an almost unlimited capacity to regenerate hair cells. This remarkable ability is possible due to the presence of neural stem/progenitor cells within neuromasts. In order to further characterize these stem cells, we use the expression of the neural progenitor markers Sox2 and Sox3, transgenic reporter lines, and morphological and topological analysis of the different cell types within the neuromast. We reveal new sub-populations of supporting cells, the sustentacular supporting cells and the neuromast stem cells. In addition, using loss-of-function and mutants of sox2 and sox3, we find that the combined activity of both genes is essential for lateral line development and regeneration. The capability of sox2/sox3 expressing stem cells to produce new hair cells, hair cell-precursors, and supporting cells after damage was analyzed in detail by time-lapse microscopy and immunofluorescence. We are able to provide evidence that sox2/3 expressing cells are the main contributors to the regenerated neuromast, and that their daughter cells are able to differentiate into most cell types of the neuromast.

scholarly journals The deltaA gene of zebrafish mediates lateral inhibition of hair cells in the inner ear and is regulated by pax2.1

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5669-5678 ◽  
Author(s):  
B.B. Riley ◽  
M. Chiang ◽  
L. Farmer ◽  
R. Heck
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Inner Ear ◽  
Cell Fate ◽  
Lateral Inhibition ◽  
Hair Cells ◽  
Fold Increase ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Hair Cell Differentiation

Recent studies of inner ear development suggest that hair cells and support cells arise within a common equivalence group by cell-cell interactions mediated by Delta and Notch proteins. We have extended these studies by analyzing the effects of a mutant allele of the zebrafish deltaA gene, deltaA(dx2), which encodes a dominant-negative protein. deltaA(dx2/dx2)homozygous mutants develop with a 5- to 6-fold excess of hair cells and a severe deficiency of support cells. In addition, deltaA(dx2/dx2) mutants show an increased number of cells expressing pax2.1 in regions where hair cells are normally produced. Immunohistological analysis of wild-type and deltaA(dx2/dx2) mutant embryos confirmed that pax2.1 is expressed during the initial stages of hair cell differentiation and is later maintained at high levels in mature hair cells. In contrast, pax2.1 is not expressed in support cells. To address the function of pax2.1, we analyzed hair cell differentiation in no isthmus mutant embryos, which are deficient for pax2.1 function. no isthmus mutant embryos develop with approximately twice the normal number of hair cells. This neurogenic defect correlates with reduced levels of expression of deltaA and deltaD in the hair cells in no isthmus mutants. Analysis of deltaA(dx2/dx2); no isthmus double mutants showed that no isthmus suppresses the deltaA(dx2) phenotype, probably by reducing levels of the dominant-negative mutant protein. This interpretation was supported by analysis of T(msxB)(b220), a deletion that removes the deltaA locus. Reducing the dose of deltaA(dx2) by generating deltaA(dx2)/T(msxB)(b220)trans-heterozygotes weakens the neurogenic effects of deltaA(dx2), whereas T(msxB)(b220) enhances the neurogenic defects of no isthmus. mind bomb, another strong neurogenic mutation that may disrupt reception of Delta signals, causes a 10-fold increase in hair cell production and is epistatic to both no isthmus and deltaA(dx2). These data indicate that deltaA expressed by hair cells normally prevents adjacent cells from adopting the same cell fate, and that pax2.1 is required for normal levels of Delta-mediated lateral inhibition.

scholarly journals Expression and Localization of Ryanodine Receptors in the Frog Semicircular Canal

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Paola Perin ◽  
Laura Botta ◽  
Simona Tritto ◽  
Umberto Laforenza
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Semicircular Canal ◽  
Ryanodine Receptors ◽  
Cell Types ◽  
Sensory Epithelium ◽  
Rt Pcr ◽  
Supporting Cells ◽  
Vesicle Recycling ◽  
Ribbon Synapses

Several experiments suggest an important role for store-released Ca2+in hair cell organs: drugs targeting IP3and ryanodine (RyRs) receptors affect release from hair cells, and stores are thought to be involved in vesicle recycling at ribbon synapses. In this work we investigated the semicircular canal distribution of RyRs by immunofluorescence, using slice preparations of the sensory epithelium (to distinguish cell types) and flat mounts of the simpler nonsensory regions. RyRs were present in hair cells, mostly in supranuclear spots, but not in supporting cells; as regards nonsensory regions, they were also localized in dark cells and cells from the ductus. No labeling was found in nerve terminals, although nerve branches could be observed in proximity to hair cell RyR spots. The differential expression of RyR isoforms was studied by RT-PCR and immunoblotting, showing the presence of RyRαin both ampulla and canal arm and RyRβin the ampulla only.

Sign in / Sign up

Export Citation Format

Share Document