Senior Research Group Leader in the Genomics Research Centre - Functional Genomics Programme

MicroRNAs (miRNAs) are key post-transcriptional regulators of cell state transitions, yet their function in early human brain development is largely unknown. Here, we present a longitudinal analysis of miRNA function in developing human forebrain organoids. We show that mRNAs and miRNAs expression mirrors known developmental gene programs and that miRNA biogenesis peaks at neural commitment. To test the function of miRNAs in regulating commitment, we impaired their biogenesis at defined stages. miRNA disruption during pre-neuronal commitment caused severe patterning defects, whereas post-commitment perturbation had minimal impact on forebrain identity. We show that miRNA loss during pre-commitment increased WNT and BMP signaling, thus shifting cell fates towards non-forebrain identity such as midbrain/hindbrain. These effects could be partially rescued by expressing five miRNAs. Our findings uncover a critical time window where miRNAs regulate morphogen signaling in early human neurodevelopment, establishing them as essential temporal determinants of cell fate and brain regional identity. ### Competing Interest Statement The authors have declared no competing interest.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

Laboratory for Molecular and Systems Biology of RNA   The Legnini Group at Human Technopole combines molecular and systems biology approaches to study gene regulation. We use synthetic biology and opt...

Carrier-assisted diffusion and cytoneme transport have been postulated to disperse Hedgehog across diverse embryonic tissues, yet their relative contributions to patterning mesenchymal tissues remains...

Makwana, Tilley et al. generate human stem cell-based trunk-like structures approximating Carnegie stage 13–14 of development. They use them to model and study the development of the thoracic and lumbar trunk.

Benzinger et al. develop a chemo-optogenetic system for precise spatiotemporal control of morphogen production in vitro. Using light-controlled Sonic hedgehog expression, they recapitulate neural tube...

Postdoc in Molecular Systems Biology

Laboratory for Molecular and Systems Biology of RNA   The Legnini Group at Human Technopole combines molecular and systems biology approaches to study gene regulation. We use synthetic biology and opt...

Laboratory for Molecular and Systems Biology of RNA   The Legnini Group at Human Technopole combines molecular and systems biology approaches to study gene regulation. We use synthetic biology and opt...