Neurocristopathies: New insights 150 years after the neural crest discovery

Abstract

The neural crest (NC) is a transient, multipotent and migratory cell population that generates an astonishingly diverse array of cell types during vertebrate development. These cells, which originate from the ectoderm in a region lateral to the neural plate in the neural fold, give rise to neurons, glia, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies (NCP) are a class of pathologies occurring in vertebrates, especially in humans that result from the abnormal specification, migration, differentiation or death of neural crest cells during embryonic development. Various pigment, skin, thyroid and hearing disorders, craniofacial and heart abnormalities, malfunctions of the digestive tract and tumors can also be considered as neurocristopathies. In this review we revisit the current classification and propose a new way to classify NCP based on the embryonic origin of the affected tissues, on recent findings regarding the molecular mechanisms that drive NC formation, and on the increased complexity of current molecular embryology techniques.

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.…”

The role of teratogens in neural crest development

“…NCPs comprise a wide variety of anomalies and syndromes that highlight the diversity of cell derivatives that the NCCs generates. They can be caused by a disruption of any of the various cellular and molecular processes that take place during NC morphogenesis (Vega‐Lopez, Cerrizuela, Tribulo, & Aybar, ). Examples include the Hirschsprung disease, characterized by an absence of enteric neurons in the enteric plexus (Amiel et al, ), the 22q11.2 deletion (DiGeorge) syndrome, which causes chronic cardiac defects (Sullivan, ), and numerous tumors originating from the NC (Maguire, Thomas, & Goldstein, ).…”

The RNA helicase DDX3 induces neural crest by promoting AKT activity

“…After the induction and subsequent maintenance, NC cells migrate out of the closing neural tube to specific destinations, where they differentiate into various types of cells and contribute to many tissues, such as the craniofacial structures, dental tissues, the peripheral nervous system, pigment cells, and cardiac tissues (Bronner and Simões-Costa, 2016;Simões-Costa and Bronner, 2015;Stuhlmiller and Garcia-Castro, 2012). In humans, impaired NC development can lead to birth defects that are collectively called neurocristopathies, including craniofacial disorders, congenital heart diseases, and pigment defects (Dubey and Saint-Jeannet, 2017;Vega-Lopez et al, 2018).…”

“…Other common symptoms include congenital heart diseases, pigment defects, and hearing/visual impairment (Snijders Blok et al, 2015;Wang et al, 2018); a recent report also suggests that these patients have high rates of neuroblastoma, a rare NC-derived childhood tumor (Lennox et al). Because this spectrum of non-CNS symptoms is typically caused by impaired NC development (Dubey and Saint-Jeannet, 2017;Vega-Lopez et al, 2018), we hypothesized that DDX3X mutations can lead to not only CNS defects but also neurocristopathies.…”