Group leader: Marion Wassef

I. Research interests:

We are interested in the modular development of the vertebrate brain. How developmental modules, neuromeres, areas subdividing the cerebral and cerebellar cortex etcÞž are individualized, how they interact, how they control their sizes independently or in relation of total brain size.

1. Evolution of telencephalic regionalization (A. Smith Fernandez)

It has been suggested that the dorsal ventricular ridge (DVR) in birds and reptiles is embryologically and functionnally related to the neocortex of mammals. The expression patterns of the region specific genes Emx-1 and Dlx1 were compared at the onset of neurogenesis in embryos of different species (chick, mouse, turtle and xenopus) and followed at later stages. In all the species studied, a phylotypic stage was detected in which the telencephalic neuroepithelum is subdivided in 3 homologous domain. We suggest that the DVR is not a neocortical homolog and that its developmental homolog in mammals is a discrete population of early generated neurons.

2. Interactions between the cerebral cortex and the basal telencephalon (C. Mÿtin, A. Bellion).

We have observed that the lateral and medial parts of the embryonic cortex differ at early stage by the length of cell cycle in the ventricular zone and by the axonal outgrowth and migration properties of their postmitotic cells. Our electrophysiological and anatomical studies have shown that GABAergic cells in the embryonic cortex express functional calcium permeable glutamate receptors . We are now studying the interactions between the glutamatergic cells in the developing cortex and cells originating in the basal telencephalon that will form the great majority of the cortical GABAergic interneurons. Cell tracing, slice grafts, cultures and time lapse videomicroscopy are used to characterise signals involved in these cellular interactions.

3. Regionalizationžand plasticity of the cerebral cortex (Y. Gitton, N. Narboux-Nême, M. Wassef)

We have used the H-2Z1 transgene as a marker of somatosensory identity to study the role of intrinsic versus extrinsic factors in the differentiation of mouse cortical areas.

We found that areal identity is acquired early, its maintenance depends on persistent cell-cell contacts but does not require thalamic afferents. During a short perinatal period expression of the H-2Z1 transgene becomes dependent on contact with thalamic axons. Whereas regional cortical identity is determined early, fragments of early cortical neuroepithelium can be induced to generate a variety of cell types that they do not produce in situ.

4. Development of the mid/hindbrain junction (L. Bally-Cuif, I. de Diego, A. Louvi, P. Alexandre, M. Wassef)

We are studying cell movements and the diffusion of signals in the mid-hindbrain domain of the neural tube in particular in early-somites-stages chick and mouse embryos around a signalling center, the isthmic organizer. At later stages, we found that subpopulations of dorsally generated hindbrain neurons rely on different cell surface or diffusible signals for their ventral migration.

II. Publications since 1998

Smith Fernandez A., Pieau C., Repÿrant J., Boncinelli E., and Wassef M. (1998). Expression of the Emx-1 and Dlx-1 genes define molecularly distinct domains in the telencephalon of mouse, chick, and turtle embryos: implications for the evolution of telencephalic subdivisions in amniotes. Development 125:2099-2111.

L. Bally-Cuif, L. Dubois and A. Vincent (1998).Molecular cloning of Zcoe2, the zebrafish homolog of Xenopus Xcoe2 and mouse EBF-2, and its expression during primary neurogenesis. Mech. Dev. 77: 85-90

Gitton Y., Cohen Tannoudji M and Wassef M. (1999) Role of thalamic axons in the expression of H-2Z1, a mouse somatosensory cortex specific marker. Cereb. Cortex 9:611-620.

Gitton Y., Cohen Tannoudji M and Wassef M. (1999) Specification of somatosensory area identity in cortical explants J. Neurosci 19:4889-4898.

Mÿtin C., Denizot J.-P., Ropert N. (2000) Intermediate zone cells express calcium-permeable AMPA receptors and establish close contact with growing axons. J Neurosci 20:696-708

Bally-Cuif L., Goutel C., Wassefž M., Wurst W., and Rosa F. (2000) Coregulation of anterior and posterior mesendodermal development by a hairy-related transcriptional repressor. Genes Dev. 14:1664-1677.

Louvi A., and Wassef M. (2000) Ectopic Engrailed-1 expression in the dorsal midline causes cell death, abnormal differentiation of circumventricular organs and errors in axonal pathfinding. Development 127:4061-4071

Tallafuss A., Wilm T.P., Crozatier M., Pfeffer P., Wassef M., and Bally-Cuif L. (2001) The zebrafish buttonhead-like gene Bts1 is an early regulator of pax2.1 expression during mid-hindbrain development. Development. 128:4021-4034.

Parenti, R., Wassef M. and Cicirata F. (2001) Expression of CRABP1 mRNA in early embryonic cerebellum. Eur J. Neurosci. 15: 1-6

Kyriakopoulou K., De Diego I., Wassef M., and Karagogeos D. (2002) A combination of chain and neurophilic migration involving the adhesion molecule TAG-1 in the caudal medulla. Development 129 : 287-296

De Diego I., Kyriakopoulou K., Karagogeos D. and Wassef M. (2002) Multiple influences on the migration of precerebellar neurons in the caudal medulla. Development 129:297-306.

Bellion A., Wassef M. and Metin C. (2002) An early partition of the mouse cerebral cortex revealed by differential cell proliferation, cell differentiation and tangential migration. submitted

III. Members of the Brain Regionalization Group (M. WASSEF)

Present members (February 2002)
Permanent research staff :
Christine Mÿtin (CR1 INSERM)	metin@wotan.ens.fr
Alessandra Pierani, (CR1 CNRS)	pierani@biologie.ens.fr from 01-01-02
Marion Wassef (DR2 CNRS)	wassef@wotan.ens.fr
PhD studentsž :
Paula Alexandre (FICT-fellow)	apalexa@wotan.ens.fr
Arnaud Bellion (ARC-fellow)	bellion@wotan.ens.fr
Nicolas Narboux-Nême (MRT-fellow)	nnarboux@wotan.ens.fr
Technical staff :
Rosette Goiame (T3 CNRS)	goiame@wotan.ens.fr
Past members
Laure Bally-Cuif	bally@gsf.de
Anibal Smith Fernandez	janibal@uma.es
Isabel de Diego Barbado	iddiego@uma.es
Yorick Gitton	gitton@saturn.med.nyu.edu
Angeliki Louvi	louvi@uchicago.edu

de gauche à droite: Paula Alexandre, Arnaud Bellion, Christine Metin, Marion Wassef, Rosette Goiame, Nicolas Narboux-Neme