Federico Calegari Lab

Long Non-Coding RNAs in Cortical Development

CRTD / DFG-Center for Regenerative Therapies Dresden - Cluster of Excellence

Fetscherstraße 105, 01307-Dresden (Germany)

Phone : +49 (0)351 458 82214
Fax :

E-Mail : federico.calegari@crt-dresden.de

Web : See online here

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 splicing. With this project we aim to dissect the molecular and cellular effects underlying the observed phenotypes and explore the role of lncRNAs and splicing in neural stem cell dynamics during brain formation.

Some key technologies for internal use :
In vivo, acute manipulation of neural stem cells in developing and adult mice including in utero electroporation, viral stereotaxic injection and their combination with inducible genetic systems (see Lange et al., 2009; Artegiani et al., 2011, 2012, 2013)

Last Publications

Aprea J and Calegari F. Long non-coding RNAs in Corticogenesis: Deciphering the Non-Coding Code of the Brain. EMBO J, 34:2865-84

Artegiani B, de Jesus Domingues AM, Bragado Alonso A, Brandl E, Massalini S, Dahl A and Calegari F. Tox: A multifunctional transcription factor and novel regulator of mammalian corticogenesis. EMBOJ, 34:896-910. Highlight in EMBO J, 37:832-4

Aprea J, Prenninger S, Dori M, Sebastian Monasor L, Wessendorf E, Zocher S, Massalini S, Ghosh T, Alexopoulou D, Lesche M, Dahl A, Groszer M, Hiller M and Calegari F. (2013) Transcriptome Sequencing During Mouse Brain Development Identifies Long Non-Coding RNAs Functionally Involved in Neurogenic Commitment. EMBO J, 32:3145-60

Artegiani B and Calegari F (2013) Lentiviruses allow widespread and conditional
manipulation of gene expression in the developing mouse brain. Development, 140:2818-22

Nonaka-Kinoshita M, Reillo I, Artegiani B, Martinez M, Nelson M, Borrell V and Calegari F (2013) Regulation of cerebral cortex size and folding by expansion of basal progenitors. EMBO J, 32:1817-28. Editor’s choice highlight by Science 340:1016 and EMBO J 32:1640

Artegiani B, Lindemann D and Calegari F (2011) Overexpression of cdk4 and cyclinD1 triggers a greater expansion of neural stem cells in the adult mouse brain. J Exp Med, 208:937-48

Lange C, Huttner WB and Calegari F (2009) Cdk4/cyclinD1 overexpression in mouse neural stem cells shortens G1, delays neurogenesis and promotes the generation and expansion of basal progenitors. Cell Stem Cell, 5:320-31. Commentary in Cell, Neurobiology Select series 139:7

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