Showing papers on "Neurocristopathy published in 2019"
TL;DR: Recent advancements in determining neural crest contributions to the ear are described, how they inform the understanding of neurocristopathies, and new avenues for further research using bioinformatic approaches are highlighted.
35 citations
TL;DR: The current knowledge of epigenetic and epitranscriptomic regulation in the development of the enteric nervous system and its potential significance for the pathogenesis of Hirschsprung’s disease are reviewed.
Abstract: Hirschsprung disease is a neurocristopathy, characterized by aganglionosis in the distal bowel. It is caused by failure of the enteric nervous system progenitors to migrate, proliferate, and differentiate in the gut. Development of an enteric nervous system is a tightly regulated process. Both the neural crest cells and the surrounding environment are regulated by different genes, signaling pathways, and morphogens. For this process to be successful, the timing of gene expression is crucial. Hence, alterations in expression of genes specific for the enteric nervous system may contribute to the pathogenesis of Hirschsprung’s disease. Several epigenetic mechanisms contribute to regulate gene expression, such as modifications of DNA and RNA, histone modifications, and microRNAs. Here, we review the current knowledge of epigenetic and epitranscriptomic regulation in the development of the enteric nervous system and its potential significance for the pathogenesis of Hirschsprung’s disease. We also discuss possible future therapies and how targeting epigenetic and epitranscriptomic mechanisms may open new avenues for novel treatment.
20 citations
TL;DR: It is found that in the absence of serum or bovine serum albumin (BSA), variability in endogenous BMP expression leads to unpredictable differentiation efficiency, and a system termed "top-down inhibition" (TDi) is developed that allows robust neural crest induction as described below.
Abstract: The neural crest is a transient embryonic tissue that originates from the border of the neural plate prior to delamination and migration throughout the developing embryo, where it contributes to a wide range of different tissues. Defects in neural crest development have been implicated in a variety of different disorders (neurocristopathies) including cancers, neuropathies, craniofacial malformations, and pigment disorders. The differentiation of human pluripotent stem cells (hPSCs) into an in vitro counterpart to neural crest cells holds huge potential for the study of neural crest development, as well as modeling neurocristopathy, carrying out drug discovery experiments and eventually cell replacement therapy. Here we describe a method for generating human neural crest cells from hPSCs that is fully defined and free from animal-derived components. We found that in the absence of serum or bovine serum albumin (BSA), variability in endogenous BMP expression leads to unpredictable differentiation efficiency. In order to control against this issue, we have developed a system termed "top-down inhibition" (TDi) that allows robust neural crest induction as described below.
4 citations
01 Jan 2019
TL;DR: Craniocaudal migration theory was presented as a classical pathogenesis of Hirschsprung’s disease (HD) by Okamoto and Ueda in 1967, showing that the human myenteric plexus was formed by neuroblasts which were distributed to the alimentary tract by craniocaudals during the fifth to the twelfth week of gestation.
Abstract: Craniocaudal migration theory was presented as a classical pathogenesis of Hirschsprung’s disease (HD) by Okamoto and Ueda in 1967, showing that the human myenteric plexus was formed by neuroblasts which were distributed to the alimentary tract by craniocaudal direction during the fifth to the twelfth week of gestation. Later, it had long been accepted that neural crest cells (NCCs) either enter the foregut mesenchyme proximally and migrate down its length in a rostral to caudal fashion (vagal NCCs) or they enter the gut at the distal end and migrate caudal to rostral (sacral NCCs). Recently, it has been proposed that transmesenteric NCCs constituted a large part of the hindgut enteric nervous system by taking a shortcut to the colon. The maldevelopment of vagal or transmesenteric NCCs is considered to be a pathogenesis of HD. The term “neurocristopathy” was presented for a category of neural crest maldevelopment by Bolande in 1974. HD is a simple neurocristopathy. There have been reported various simple nonneoplastic and neoplastic neurocristopathies. Complex neurocristopathies associated with HD include Waardenburg syndrome type 4 (Waardenburg-Shah syndrome), neuroblastoma, multiple endocrine neoplasia type 2, congenital central hyperventilation, and others. It is important to screen an association of nonneoplastic and neoplastic neurocristopathies in patients who have a neurocristopathy.