The combination of transcriptomics and informatics identifies pathways targeted by miR-204 during neurogenesis and axon guidance

Ivan Conte, Stefania Merella, Jose Manuel Garcia-Manteiga, Chiara Migliore, Dejan Lazarevic, Sabrina Carrella, Raquel Marco-Ferreres, Raffaella Avellino, Nathan Paul Davidson, Warren Emmett, Remo Sanges, Nicholas Bockett, David Van Heel, Germana Meroni, Paola Bovolenta, Elia Stupka, Sandro Banfi

Research output: Contribution to journalArticle

Abstract

Vertebrate organogenesis is critically sensitive to gene dosage and even subtle variations in the expression levels of key genes may result in a variety of tissue anomalies. MicroRNAs (miRNAs) are fundamental regulators of gene expression and their role in vertebrate tissue patterning is just beginning to be elucidated. To gain further insight into this issue, we analysed the transcriptomic consequences of manipulating the expression of miR-204 in the Medaka fish model system. We used RNA-Seq and an innovative bioinformatics approach, which combines conventional differential expression analysis with the behavior expected by miR-204 targets after its overexpression and knockdown. With this approach combined with a correlative analysis of the putative targets, we identified a wider set of miR-204 target genes belonging to different pathways. Together, these approaches confirmed that miR-204 has a key role in eye development and further highlighted its putative function in neural differentiation processes, including axon guidance as supported by in vivo functional studies. Together, our results demonstrate the advantage of integrating next-generation sequencing and bioinformatics approaches to investigate miRNA biology and provide new important information on the role of miRNAs in the control of axon guidance and more broadly in nervous system development.

Original languageEnglish
Pages (from-to)7793-7806
Number of pages14
JournalNucleic Acids Research
Volume42
Issue number12
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Genetics

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    Conte, I., Merella, S., Garcia-Manteiga, J. M., Migliore, C., Lazarevic, D., Carrella, S., Marco-Ferreres, R., Avellino, R., Davidson, N. P., Emmett, W., Sanges, R., Bockett, N., Van Heel, D., Meroni, G., Bovolenta, P., Stupka, E., & Banfi, S. (2014). The combination of transcriptomics and informatics identifies pathways targeted by miR-204 during neurogenesis and axon guidance. Nucleic Acids Research, 42(12), 7793-7806. https://doi.org/10.1093/nar/gku498