Bhaval Parmar

Neural crest cells (NCCs) are a population of multipotent cells that undergo specification, epithelial-to-mesenchymal transition, migration and differentiation into a plethora of cell types. A wealth of studies across various embryonic model systems have established a dogma as to the molecular mechanisms and signaling cascades that contribute to NCC development. While Wnt, FGF and BMP signaling pathways have well-established and essential roles in several aspects of NCC development, the Hedgehog (HH) signaling pathway has received limited attention for any specific role in this process. Herein, we propose two distinct, temporal roles for the transcription factor GLI3 in NCC development. Gli3, and other members of the HH pathway, were robustly co-expressed with established NCC induction and specification markers in chick, mouse and human embryonic stem cell-derived NCCs. Early knockdown of GLI3 reduced expression of key markers of NCC specification and conditional knockout of Gli3 post-specification specifically impaired the ability of cranial NCCs to differentiate into ectomesenchymal derivatives. Together, these results demonstrate dual roles for GLI3 in early NCC specification and later in cranial NCC differentiation.

Flubendiamide, a phthalic acid diamide insecticide, has been implicated in potential teratogenic effects on non‐target organisms, especially during embryonic development. This study examines the impact of flubendiamide on eye development in chick embryos, a well‐established model for vertebrate development. Exposure to 0.5 µg/µL of flubendiamide significantly impaired early ocular morphogenesis, resulting in severe defects such as underdeveloped optic cups and the absence of lens and corneal structures. Histopathological analysis demonstrated disrupted optic cup differentiation, while in silico docking studies revealed strong interactions between flubendiamide and key oculogenic proteins, including OTX2, PAX6, and SOX2. These interactions were associated with altered expression patterns of these critical regulators, alongside overexpression of SHH and downregulation of BMP4, BMP7, and FGF8, which are essential for optic vesicle formation and lens differentiation. Additionally, increased CASPASE‐3 expression indicated enhanced apoptosis, contributing to the observed ocular anomalies. These findings suggest that flubendiamide disrupts key signaling pathways necessary for proper eye development, potentially leading to congenital eye defects. The study highlights the need for a thorough evaluation of the molecular mechanisms driving flubendiamide‐induced teratogenicity to ensure safer pesticide use and protect environmental and human health.