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NEURAL CREST TRANSCRIPTOME SCREEN IDENTIFIES NOVEL GENETIC REGULATORS IN CRANIOFACIAL DEVELOPMENT
Presenter: Yawei Kong, PhD
Co-Authors: Grimaldi M; Liao EC
Massachusetts General Hospital Harvard Medical School

Background: Cranial neural crest (CNC) cells migrate and elaborate into craniofacial structures, dysregulation of which leads to craniofacial malformations. Many of the intrinsic genetic programs regulating CNC fate commitment and morphogenesis remain largely unknown. Using comparative transcriptome analysis between premigration (10 somites) and postmigration (24 hpf) CNC cells, we aimed to segregate the early migrating genes from those in late pharyngeal morphogenesis. We utilized the zebrafish model to carry out high-throughput expression and function analysis and identified novel genes that modulate CNC development.

Methods: Pre vs. post-migration CNC cells were isolated from Tg(sox10::egfp) embryos via FACS. Gene expression profiling was analyzed by Affymetrix gene-chip. Spatiotemporal expression of genes of interest was triaged by high-throughput wholemount RNA in situ hybridization (WISH). Morpholino-mediated gene knockdown was performed to assess gene function.

Results: 408 transcripts differentially expressed ? 1.5-fold between pre and post-migration CNC cells were identified in microarray triplicates. Of these, 237 (58%) showed high expression in premigration CNC, and 171 (42%) are enriched in postmigration CNC. Candidate genes with pharyngeal expression were further screened by WISH. Developmentally upregulated genes include: icn, s100a10b, aqp3, which labels lower jaw structures; cTGF≤a marks the extending maxillary prominence and trabecula in upper jaw. Meanwhile, irx7 expression was detected along the neural tube at early migration but was downregulated and restricted to specific CNC streams.

Conclusion: Transcriptome comparison between pre and post-migratory CNC revealed a highly dynamic transcriptional profile, and most notably irx7 was identified as a pivotal gene in regulating craniofacial development.


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