Neural crest contributions to the ear: Implications for congenital hearing disorders

Abstract

Congenital hearing disorders affect millions of children worldwide and can significantly impact acquisition of speech and language. Efforts to identify the developmental genetic etiologies of conductive and sensorineural hearing losses have revealed critical roles for cranial neural crest cells (NCCs) in ear development. Cranial NCCs contribute to all portions of the ear, and defects in neural crest development can lead to neurocristopathies associated with profound hearing loss. The molecular mechanisms governing the development of neural crest derivatives within the ear are partially understood, but many questions remain. In this review, we describe recent advancements in determining neural crest contributions to the ear, how they inform our understanding of neurocristopathies, and highlight new avenues for further research using bioinformatic approaches.

Noncoding microdeletion in mouseHgfdisrupts neural crest migration into the stria vascularis, reduces the endocochlear potential and suggests the neuropathology for human nonsyndromic deafness DFNB39

“…The preferential reduction of Hgf in the cochlea in the case of the del10 mutation coupled with the confinement of differentially expressed genes to melanocyte-specific genes and pathways also suggest that the effect of the Hgf del10 mutation may be confined to the cochlea. Thus, this mutation appears to represent a unique situation, since neurocristopathies most often result in syndromes involving multiple organ systems (Bolande, 1974; Vega-Lopez et al, 2018; Ritter and Martin, 2019).…”

“…Homozygosity for the del10 mutation results in a failure of neural crest-derived melanocytes to incorporate into the SV during development, leading to a reduced intermediate cell layer and consequently, compromised endocochlear potential (EP), deafness and subsequent hair cell loss. Thus, DFNB39 qualifies as a neurocristopathy that is surprisingly nonsyndromic (Bolande, 1974; Vega-Lopez et al, 2018; Ritter and Martin, 2019). Mouse models described here provide an opportunity to study the role of HGF-MET signaling in neural crest cell incorporation into the SV.…”

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

“…Whether other cell types in the SV derive from neural crest cells remains to be determined by further lineage tracing experiments and have not been shown in more recent lineage tracing experiments (Shibata et al, 2016). The contribution of neurocristopathies to hearing loss is a developing area of research (Hao et al, 2014;Locher et al, 2015;Shibata et al, 2016;Ritter and Martin, 2019). Another example of hearing loss where multiple cell types may be affected includes Connexin 26 and 30 encoded by Gjb2 and Gjb6, respectively, which appear to be expressed in intermediate and basal cells and, to a lesser extent, marginal cells ( Figure 10) (Lang et al, 2007;Nickel and Forge, 2008;Liu et al, 2009;Mei et al, 2017).…”

Noncoding Microdeletion in MouseHgfDisrupts Neural Crest Migration into the Stria Vascularis, Reduces the Endocochlear Potential, and Suggests the Neuropathology for Human Nonsyndromic Deafness DFNB39

“…The preferential reduction of Hgf in the cochlea in the case of the del10 mutation coupled with the confinement of DEGs to melanocyte-specific genes and pathways also suggests that the effect of the Hgf del10 mutation may be confined to the cochlea. Thus, this mutation appears to represent a unique situation, since neurocristopathies most often result in syndromes involving multiple organ systems (Bolande, 1974;Vega-Lopez et al, 2018;Ritter and Martin, 2019).…”