PT  - JOURNAL ARTICLE
AU  - Goldsworthy, Sian
AU  - Losa, Marta
AU  - Bobola, Nicoletta
AU  - Griffiths-Jones, Sam
TI  - MicroRNA miR-92b-3p regulation of a cardiovascular gene regulatory network in the developing branchial arches
AID  - 10.1101/2024.07.28.605500
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.07.28.605500
4099  - http://biorxiv.org/content/early/2024/07/29/2024.07.28.605500.short
4100  - http://biorxiv.org/content/early/2024/07/29/2024.07.28.605500.full
AB  - Vertebrate branchial arches (BAs) are a developmental paradigm, undergoing coordinated differentiation and morphogenesis to form various adult derivative tissues. MicroRNAs can strengthen gene regulatory networks (GRNs) to promote developmental stability. To interrogate the contribution of microRNAs to BA development, we generated a novel microRNA-sequencing dataset from mouse BAs. We identified 550 expressed microRNAs, of which approximately 20% demonstrate significant differential expression across BA domains. The three most posterior BAs and the connecting outflow tract (PBA/OFT) are enriched in biological processes linked to cardiovascular development. We identified enriched predicted microRNA-target interactions with PBA/OFT upregulated cardiovascular genes and validated transcripts encoding for two fundamental cardiac transcription factors (TFs), Gata6 and Tbx20, as targets of miR-92b-3p. Furthermore, we demonstrated that miR-92b-3p can downregulate endogenous GATA6 and TBX20 in human embryonic stem cells (hESCs) undergoing cardiomyocyte differentiation, consistent with conservation of these microRNA-target interactions in a cardiogenic setting. miR-92b-3p has previously been shown to target two other cardiac TFs, Hand2 and Mef2D. Therefore, we hypothesise that miR-92b-3p acts to stabilise cardiovascular GRNs during PBA/OFT development, through acting in multiple microRNA-mediated coherent feedforward loops.Competing Interest StatementThe authors have declared no competing interest.Fastq files corresponding to small RNA-sequencing libraries are available from the European Nucleotide Archive: ERR12176799 BA1_E10.5_Rep1, ERR12176800 BA2_E10.5_Rep1, ERR12176801 PBA_E10.5_Rep1, ERR12176802 BA1_E10.5_Rep2, ERR12176803 BA2_E10.5_Rep2, ERR12176804 PBA_E10.5_Rep2, ERR12176805 BA1_E11.5_Rep1, ERR12176806 BA2_E11.5_Rep1, ERR12176807 PBA_E11.5_Rep1, ERR12176808 BA1_E11.5_Rep2, ERR12176809 BA2_E11.5_Rep2, ERR12176810 PBA_E11.5_Rep2.