Neural Development

Research Interests

The main research program of the Developmental Biology Group aims to investigate the basic molecular mechanisms that regulate the production of nerve cells in vertebrate embryos

Group Members

Research Project

Cell Fate and Cell Polarity within the vertebrate embryonic neuroepithelium

A major research focus in our lab concerns how cell polarity is established in the neural epithelium and how it contributes to cell fate decisions during neural development. In Drosophila, it has been shown that neural progenitors can divide asymmetrically, generating daughter cells with different fates. In vertebrates, it has been suggested that similar mechanisms can control the acquisition of different fates by dividing neuroepithelial cells during neurogenesis. We have investigated this issue in the chick embryo, looking at the orientation of mitotic spindles in dividing neuroepithelial cells of the spinal cord, using fixed specimens and time-lapse microscopy. No correlation between the axis of division and the fate of the daugther cells could be infered: at any time, the great majority of neuroepithelial cells divide within the plane of the epithelium, with only a minor fraction dividing along the apico-basal axis. Also, chick homologues of Drosophila polarity proteins, which are asymmetrically segregated during neuroblast divisions, don’t reveal a polarized apico-basal distribution in dividing neuroepithelial cells. Our findings, therefore, do not support a role for intrinsically controlled, asymmetric divisions during vertebrate neurogenesis. We have also found that the PAR polarity complex (PAR3, PAR6 and aPKC) is specifically localized at adherens junctions of neuroepithelial cells. Misexpression of the PAR3 protein in the chick embryonic neural tube leads to a profound disturbance of the neuroepithelium, with loss of normal apico-basal polarity and appearance of “ectopic” cell junctions. This leads to the formation of characteristic neuroepithelial aggregates (“rosettes”) within the neuroepithelium. We are currently trying to understand how this phenotype develops and how it affects the normal process of neurogenesis. A role for the Planar Cell Polarity (PCP) pathway in the developing nervous system is also being studied in the lab. We have characterized several homologues of the Drosophila PCP genes and are currently analysing their function in the chick embryo. Another research program in the lab aims to investigate the basic molecular mechanisms that regulate the production of nerve cells in vertebrate embryos, in particular the role of the Delta/Notch signalling pathway in cell fate decisions within the developing nervous system. We are studying how different Notch ligands contribute to the regulation of neuronal production in the embryo, from neural precursor division until the acquisition of the differentiated characteristics of neuronal cells. We are studying these processes in the chick neural retina, taking advantage of our experience with manipulating Notch activity in this tissue, using both retrovirus and electroporation. Finally, we are studying the process of neuronal commitment and differentiation using mouse ES cells, trying to understand the molecular controls that regulate the in vitro production of neurons from ES cells.

Collaborators

Stowers Institute, Kansas City, USA
Olivier Pourquié

Universidad Pompeu Fabra, Barcelona, Spain
Fernando Giraldez

Instituo Alberto SOls, Univ. Autónoma, Madrid, Spain
Isabel Varela

École Normale Supérieure, Paris, France
François Schweisguth

Publications

Kawakami, Y., Rodriguez-Leon, J., Koth, C., Büschen, D., Itoh, T., Raya,A., Ng, J., Esteban, C., Henrique, D., Takahashi,S., Asahara, H., Belmonte, J.C. (2003). MKP3 Mediates the Cellular Response to FGF8 Signalling in the Vertebrate Limb. Nature Cell Biology 5 :513-19

Henrique, D., Schweisguth, F. (2003). Cell Polarity: the ups and downs of the Par6-aPKC complex. Current Oppinion on Genetics & Development 13 :341-350

Bekman, E., Henrique, D. (2002). Embryonic expression of three murine genes with homology to the Drosophila prickle gene. Mechanisms of Development 119 :77-81