Gene–environment interactions in the pathogenesis of common craniofacial anomalies

Fitriasari, Sharien; Trainor, Paul A.

doi:10.1016/bs.ctdb.2022.10.005

Cited by 3 publications

(1 citation statement)

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“…Although NC cells emerge all along the anteroposterior axis and are sculpted into discrete streams that invade immature extracellular matrix (ECM) and loose mesoderm, the molecular mechanisms that underlie invasion and collective cell migration remain unclear. Mistakes in NC cell migration led to birth defects, termed neurocristopathies, that include shortened lower jaw and cleft lip and palate in the head, and failure to reach the end of the embryonic gut or Hirschsprung’s disease (Vega-Lopez et al, 2018; Fitriasari and Trainor, 2023). Therefore, by leveraging the accessibility of the neural crest to advances in spatial gene profiling and their ancestral relationship to melanoma, identification and functional analysis of a critical set of cell invasion genes have the potential to inform strategies to repair human neurocristopathies and control cancer metastasis.…”

Section: Introductionmentioning

confidence: 99%

Identification of Neural Crest and Neural Crest-Derived Cancer Cell Invasion and Migration Genes Using High-throughput Screening and Deep Attention Networks

Kasemeier-Kulesa,

Martina Perez,

Baker

et al. 2024

Preprint

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Background: Cell migration and invasion are well-coordinated processes in development and disease but remain poorly understood. We previously showed that highly migratory neural crest (NC) cells share a 45-gene panel with other cell invasion phenomena, including cancer. To identify critical genes of the 45-gene panel, we performed a high-throughput siRNA screen and used statistical and deep learning methods to compare NC- versus non-NC-derived human cell lines. Results: We find 14 out of 45 genes significantly reduces c8161 melanoma cell migration; only 4 are shared with HT1080 fibrosarcoma cells (BMP4, ITGB1, KCNE3, RASGRP1). Deep learning attention network analysis identified distinct cell-cell interaction patterns and significant alterations after BMP4 or RASGRP1 knockdown in c8161 cells. Addition of recombinant proteins to the culture media identified 5 out of the 10 known secreted molecules stimulate c8161 cell migration, including BMP4. BMP4 siRNA knockdown inhibited c8161 cell invasion in vivo and in vitro; however, its addition to the culture media rescued c8161 cell invasion. Conclusion: A high-throughput screen and deep learning rapidly distilled a 45-gene panel to a small subset of genes that appear critical to melanoma cell invasion and warrant deeper in vivo functional analysis for their role in driving the neural crest.

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Section: Introductionmentioning

confidence: 99%