Long Non-Coding RNAs and Alternative Splicing Control Cortical Development

• Applicant: Professor Federico Calegari, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Developmental Neurobiology
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258396983

Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify the molecular mechanisms regulating the switch from proliferation to differentiation. However, analysing transcriptomes of individual cell types in complex tissues remains a challenge. We generated a RFP/GFP double-reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations in the developing brain. Transcriptome sequencing of the three cell types revealed numerous uncharacterized protein-coding genes as well as long non-coding (lnc)RNAs with highly specific and transient expression patterns and characterizing the signature of neurogenic commitment. In vivo manipulation of one such lncRNA strongly influenced neural stem cell differentiation and neuronal survival during corticogenesis likely through a regulation of alternative splicing. With this project we aim to dissect the molecular and cellular effects underlying the observed phenotypes and explore the role of alternative splicing in neural stem cell dynamics during brain formation.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1738: Emerging Roles of Non-Coding RNAs in Nervous System Development, Plasticity and Disease