Neural crest cell motility in valproic acid

Grouping of histone deacetylase inhibitors and other toxicants disturbing neural crest migration by transcriptional profiling

“…Disturbance of such migration events can lead to severe malforma tions or diseases including Hirschsprung disease, Teratology of Fallot or DiGeorge syndrome in humans (Keyte and Hutson, 2012;Menendez et al, 2013). Impairment of NC development and function after exposure to a variety of chemicals, including pesticides, planar PCBs or anticonvulsant drugs has been observed in different vertebrate test systems (Di Renzo et al, 2007;Fuller et al, 2002;Grimes et al, 2008;Menegola et al, 2005a;Papis et al, 2006). Such animal based test systems are very limited in their throughput.…”

“…Defects in neural crest function and differentiation can lead to severe birth defects and diseases such as cleft palate, Hirschsprung disease or CHARGE syndrome (Keyte and Hutson, 2012). Several chemicals are known to disturb the NCC development and migration and thereby cause developmental defects (Di Renzo et al, 2007;Fuller et al, 2002;Menegola et al, 2000). A comprehensive hazard assessment approach requires therefore test systems that detect disturbances of NCC function.…”

Attenuation of Phospholipid Signaling Provides a Novel Mechanism for the Action of Valproic Acid

“…In support of this, Denlinger et al (10) recently found that the combined inhibition of PI3K and HDAC induced lung cancer cell apoptosis in vitro and in vivo. Secondly, it may suppress tumor metastasis (4) by inhibiting chemotaxis, and VPA has also been shown to inhibit chemotaxis in basic fibroblast growth factor-induced human umbilical vein endothelial cell migration (37) and to reduce individual neural crest cell migration (13). It is also interesting that the role of PIP 2 is increasingly being recognized in cell migration (28).…”

Design of a high-throughput human neural crest cell migration assay to indicate potential developmental toxicants_suppl

“…They comprise the anti-epileptic drug valproic acid (found to interfere with NCC migration out of chick neural tube explants, Fuller et al, 2002) and the triazole and FGF8 for another seven days, cells were live-stained for human natural killer-1 (HNK-1, monoclonal anti-human CD57/ HNK-1 antibody, Sigma-Aldrich) and FACS-sorted for positive expression of HNK-1 and negative expression of Dll1 using a BD FACSAria IIIu (BD Biosciences). The sorted cells were expanded in N2-S medium, consisting of DMEM/F12 (Gibco) and supplemented with 100 µg/ml apotransferrin, 25 µg/ml insulin, 8.6 mM glucose, 100 μM putrescine, 30 nM selenite, 20 nM progesterone (all purchased from Sigma-Aldrich), 1x GlutaMax and 1% penicillin/streptomycin (both from Gibco), 20 ng/ml epidermal growth factor (EGF) and 20 ng/ml FGF2 (both from R&D).…”

“…However, only few assays that test NCC function have been developed. Some of these tests use ex vivo neural tube explants (Fuller et al, 2002;Bergeron et al, 2013;Usami et al, 2014Usami et al, , 2015, but this only allows low throughput testing and the data-analysis is very time-consuming. Furthermore, the use of animal cells might not be relevant for human toxicity, as there are tremendous species differences in the timing of epithelial-to-mesenchymal transition, delamination and migration of NCCs as well as the closure of the neural tube (Theveneau and Mayor, 2012).…”