The role of teratogens in neural crest development

Abstract

The neural crest (NC), discovered by Wilhelm His 150 years ago, gives rise to a multipotent migratory embryonic cell population that generates a remarkably diverse and important array of cell types during the development of the vertebrate embryo. These cells originate in the neural plate border (NPB), which is the ectoderm between the neural plate and the epidermis. They give rise to the neurons and glia of the peripheral nervous system, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies are a class of congenital diseases resulting from the abnormal induction, specification, migration, differentiation or death of NC cells (NCCs) during embryonic development and have an important medical and societal impact. In general, congenital defects affect an appreciable percentage of newborns worldwide. Some of these defects are caused by teratogens, which are agents that negatively impact the formation of tissues and organs during development. In this review, we will discuss the teratogens linked to the development of many birth defects, with a strong focus on those that specifically affect the development of the NC, thereby producing neurocristopathies.Although increasing attention is being paid to the effect of teratogens on embryonic development in general, there is a strong need to critically evaluate the specific role of these agents in NC development. Therefore, increased understanding of the role of these factors in NC development will contribute to the planning of strategies aimed at the prevention and treatment of human neurocristopathies, whose etiology was previously not considered.

PIWI-interacting RNA sequencing profiles in maternal plasma-derived exosomes reveal novel non-invasive prenatal biomarkers for the early diagnosis of nonsyndromic cleft lip and palate

“…For example, in addition to the spinal ganglia, neural crest cells were shown to be involved in the building of craniofacial and cardiac regions [44]. Second, a review provided a uniquely comprehensive view of the teratogens linked to the development of the above congenital malformations and revealed several shared multifactorial causes, such as maternal folate deficiency, gestational diabetes, and retinoic acid [45]. Finally, it should be noted that CHDs and nsCLP are also often found together, which illustrates the variety of neurocristopathy associations.…”

Neurogenesis From Neural Crest Cells: Molecular Mechanisms in the Formation of Cranial Nerves and Ganglia

“…The NC is one of the most important features that separate vertebrates from other chordate organisms. It arises at the posterior and lateral borders of the neural and non-neural ectoderm, the neural plate border (Figure 1) (Cerrizuela et al, 2020).…”

The crucial role of model systems in understanding the complexity of cell signaling in human neurocristopathies

“…Since NCPs are complex and chronic medical conditions, their pharmacological intervention might require taking advantage of a combination of tools and strategies within a range of animal models. As to the environmental causality of NCPs (Cerrizuela et al, 2020), it would be interesting to establish whether multiple teratogens can be rated based on the severity of their biochemical and functional consequences on NC cell signaling pathway‐dependent developmental events to warn the public against their use.…”

“…NCPs can be classified according to the temporal window in which the alteration occurs, that is, during the induction, specification, migration, and/or differentiation of the affected NC population (Etchevers et al, 2006). However, a recent classification takes into account the axial origin of the affected NC population, thus simplifying the interpretation of both affected organs or tissues in the patient and the causal origin of the NCPs, considering also numerous novel mechanisms through which these diseases arise, for example, ciliopathies, ribosomopathies, epigenetics, and environmental effects (Cerrizuela et al, 2020; Vega‐Lopez et al, 2018). A key player in understanding the origin and the underlying mechanisms of human NCPs is the research carried out in animal models (McGonigle & Ruggeri, 2014).…”