Building and shaping the central nervous system in higher vertebrates
The generation and morphogenesis of the neural plate is of tremendous fundamental and clinical importance (neural-tube defects occur in humans at about 1 per 1000 pregnancies). The main focus in my laboratory is on deciphering the mechanisms of this process in higher vertebrates. In particular, we aim at understanding the following key aspects:
1) What are the individual cell behaviours underlying the morphogenesis of the early neural plate, and how are they controlled and orchestrated in terms of tissue interactions and molecular control?
2) How do the naturally occurring stem cells function to build the main embryonic axis, including the neural plate? What are their modes of renewal and lineage relationships, and how are they established?
Our experimental approaches combine multi-photon, high-resolution imaging in intact embryos (Nature 449: 1049) with precisely controlled gene-targeting methods (Nat Protoc 3: 410) and embryological manipulations in the chick embryo. We are also using computer simulations to integrate the data from these reductionist approaches into a complete model. Ultimately, we aim to understand the shaping of the neural tissue and of the entire embryo.
Current members (from October 2011)
Dr Sabine Knipp
Dr Mansoor Raza
Ismahan Suleiman (PhD student)
Katherine Gist (Part II PDN)
2009-10: Dr Elena Tzouanacou, Sophie J Donkin (Part II
2010-11: Christoph Budjan (1st year WT PhD programme), Ismahan Suleiman (1st year MRC PhD programme), Snigdha M Reddy & Emily C Bottle (Part II Neuroscience)
Summer students: Laia Muñoz (U Barcelona, 2010), Snigdha M Reddy (U Cambridge, 2011)
Voiculescu O, Stern CD (2011). High-Resolution, multiphoton time-lapse imaging of early chick embryos. In Imaging in Developmental Biology: A Laboratory Manual (J Sharpe, R Wong, R Yuste (eds.)), Ch. 40, pp. 581-92. Cold Spring Harbor Laboratory Press, 2011.
Voiculescu O#*, Papanayotou C*, Stern CD# (2008). Spatially- and temporally-controlled electroporation of early chick embryos for gain- and loss-of-function experiments. Nature Protocols 3(3): 419-26. pdf, supplementary information
Voiculescu O#, Bertocchini F, Wolpert L, Keller RE, Stern CD# (2007). The amniote primitive streak is defined by epithelial cell intercalation before gastrulation. Nature 449:1049-52. pdf, supplementary information
Maro GS*, Vermeren M*, Voiculescu O, Melton L, Cohen J, Charnay P, Topilko P (2004). Neural crest boundary cap cells constitute a source of neuronal and glial cells of the PNS. Nat Neurosci 7(9): 930-8. pdf
Chatonnet F, del Toro ED, Voiculescu O, Charnay P, Champagnat J (2002). Different respiratory control systems are affected in homozygous and heterozygous kreisler mutant mice. Eur J Neurosci 15: 684-92. pdf
Voiculescu O, Taillebourg, E, Pujades C, Kress C, Buart S, Charnay P, Schneider-Maunoury S (2001). Hindbrain patterning: Krox-20 couples segmentation and specification of regional identity. Development 128: 4967-78. pdf
Gambardella L, Schneider-Maunoury S, Voiculescu O, Charnay P, Barrandon Y (2000). Pattern of expression of the transcription factor Krox-20 in mouse hair follicle. Mech Dev 96: 215-8. pdf
Voiculescu O, Charnay P, Schneider-Maunoury S (2000). Expression pattern of a Krox-20/Cre knock-in allele in the developing hindbrain, bones, and peripheral nervous system. Genesis 26: 123-6. pdf
Garratt AN, Voiculescu O, Topilko P, Charnay P, Birchmeier C (2000). A dual role of erbB2 in myelination and in expansion of the Schwann cell precursor pool. J Cell Biol 148: 1035-46. pdf
Mathis L, Sieur J, Voiculescu O, Charnay P, Nicolas JF (1999). Successive patterns of clonal cell dispersion in relation to neuromeric subdivision in the mouse neuroepithelium. Development 126: 4095-106. pdf
(# corresponding author; * equal contribution)
The neural plate of the chick
Genetic manipulations in the chick embryo: expression plasmid vectors (left column, red) or morpholino DNA (right column, green) can be introduced with spatial and temporal control (from Voiculescu et al. Nat Protoc 2008).
Imaging the chick embryo (from Voiculescu et al. Nature 2007).