Where hearing starts: the development of the mammalian cochlea

Basch, Martín L.; Brown, Rogers M.; Jen, Hsin-I; Groves, Andrew K.

doi:10.1111/joa.12314

Cited by 108 publications

(104 citation statements)

References 243 publications

(640 reference statements)

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“…Interestingly, other neurogenic transcription factors that regulate ganglion formation (Neurog1 and NeuroD) have also been implicated in the development of cochlear hair cells, including potentially the spatial arrangement and/or differentiation of IHCs and OHCs (Fritzsch et al, 2002; Fritzsch et al, 2011; Jahan et al, 2010a; Jahan et al, 2010b; Jahan et al, 2015b; Ma et al, 1998; Matei et al, 2005), although some believe this is due to their effects in the neurons, not to a direct action in cells of the organ or Corti (Basch et al, 2015; Bok et al, 2013; Tateya et al, 2013). NeuroD, which like Insm1 is expressed in delaminating progenitors, also appears to be expressed in nascent hair cells, although this expression is not restricted to OHCs (Fritzsch et al, 2006; Matei et al, 2005; Scheffer and Shen, 2015), as is the expression of Insm1 .…”

Section: Discussionmentioning

confidence: 99%

Insm1 promotes neurogenic proliferation in delaminated otic progenitors

Lorenzen

Duggan

Osipovich

et al. 2015

Mechanisms of Development

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INSM1 is a zinc-finger protein expressed throughout the developing nervous system in late neuronal progenitors and nascent neurons. In the embryonic cortex and olfactory epithelium, Insm1 may promote the transition of progenitors from apical, proliferative, and uncommitted to basal, terminally-dividing and neuron producing. In the otocyst, delaminating and delaminated progenitors express Insm1, whereas apically-dividing progenitors do not. This expression pattern is analogous to that in embryonic olfactory epithelium and cortex (basal/subventricular progenitors). Lineage analysis confirms that auditory and vestibular neurons originate from Insm1-expressing cells. In the absence of Insm1, otic ganglia are smaller, with 40% fewer neurons. Accounting for the decrease in neurons, delaminated progenitors undergo fewer mitoses, but there is no change in apoptosis. We conclude that in the embryonic inner ear, Insm1 promotes proliferation of delaminated neuronal progenitors and hence the production of neurons, a similar function to that in other embryonic neural epithelia. Unexpectedly, we also found that differentiating, but not mature, outer hair cells express Insm1, whereas inner hair cells do not. Insm1 is the earliest known gene expressed in outer versus inner hair cells, demonstrating that nascent outer hair cells initiate a unique differentiation program in the embryo, much earlier than previously believed.

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Section: Discussionmentioning

confidence: 99%

Insm1 promotes neurogenic proliferation in delaminated otic progenitors

Lorenzen

Duggan

Osipovich

et al. 2015

Mechanisms of Development

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“…Its sensory organ, the organ of Corti, contains mechanosensory inner and outer hair cells, surrounded by different types of supporting cells (Kelley et al, 2009; Basch et al, 2016). The organ of Corti is bounded by two populations of non-sensory epithelium, the inner and outer sulci.…”

Section: Introductionmentioning

confidence: 99%

Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates

Basch

Brown

Jen

et al. 2016

eLife

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The signals that induce the organ of Corti and define its boundaries in the cochlea are poorly understood. We show that two Notch modifiers, Lfng and Mfng, are transiently expressed precisely at the neural boundary of the organ of Corti. Cre-Lox fate mapping shows this region gives rise to inner hair cells and their associated inner phalangeal cells. Mutation of Lfng and Mfng disrupts this boundary, producing unexpected duplications of inner hair cells and inner phalangeal cells. This phenotype is mimicked by other mouse mutants or pharmacological treatments that lower but not abolish Notch signaling. However, strong disruption of Notch signaling causes a very different result, generating many ectopic hair cells at the expense of inner phalangeal cells. Our results show that Notch signaling is finely calibrated in the cochlea to produce precisely tuned levels of signaling that first set the boundary of the organ of Corti and later regulate hair cell development.DOI: http://dx.doi.org/10.7554/eLife.19921.001

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“…To generate inner ear tissue, whether in organoids or in a microfluidic system, early developmental processes are of importance from the onset of organoid culture. The early period of inner ear development has been excellently reviewed and hence, within the scope of organoid generation, we will briefly focus on the early regionalization of the ectoderm and the later specification of placodal‐derived cell types (Ohyama et al, ; Patthey et al, ; Moody and LaMantia, ; Basch et al, ).…”

Section: Focussing On the Inner Earmentioning

confidence: 99%

Building an Artificial Stem Cell Niche: Prerequisites for Future 3D‐Formation of Inner Ear Structures—Toward 3D Inner Ear Biotechnology

Groot

Sliedregt

Benthem

et al. 2019

The Anatomical Record

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In recent years, there has been an increased interest in stem cells for the purpose of regenerative medicine to deliver a wide range of therapies to treat many diseases. However, two‐dimensional cultures of stem cells are of limited use when studying the mechanism of pathogenesis of diseases and the feasibility of a treatment. Therefore, research is focusing on the strengths of stem cells in the three‐dimensional (3D) structures mimicking organs, that is, organoids, or organ‐on‐chip, for modeling human biology and disease. As 3D technology advances, it is necessary to know which signals stem cells need to multiply and differentiate into complex structures. This holds especially true for the complex 3D structure of the inner ear. Recent work suggests that although other factors play a role, the extracellular matrix (ECM), including its topography, is crucial to mimic a stem cell niche in vitro and to drive stem cells toward the formation of the tissue of interest. Technological developments have led to the investigation of biomaterials that closely resemble the native ECM. In the fast forward moving research of organoids and organs‐on‐chip, the inner ear has hardly received attention. This review aims to provide an overview, by describing the general context in which cells, matrix and morphogens cooperate in order to build a tissue, to facilitate research in 3D inner ear technology. Anat Rec, 303:408–426, 2020. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

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Where hearing starts: the development of the mammalian cochlea

Cited by 108 publications

References 243 publications

Insm1 promotes neurogenic proliferation in delaminated otic progenitors

Insm1 promotes neurogenic proliferation in delaminated otic progenitors

Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates

Building an Artificial Stem Cell Niche: Prerequisites for Future 3D‐Formation of Inner Ear Structures—Toward 3D Inner Ear Biotechnology

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