Molecular Basis of Brain Morphogenesis in Vertebrate Embryos
C. Redies - Publications in Molecular Neuroembryology
Recent Collaborations:
• Dr. Frans van Roy, Dr. K. Vanhalst, Ghent University, Belgium• Drs. L. Puelles, L. Medina, P. Aroca, University of Murcia, Spain
• Dr. S. Hirano, Dr. M. Takeichi, RIKEN Center for Dev. Biology, Kobe, Japan
• Dr. Harald Luksch, RWTH Aachen, Germany
Research Report
We are studying the expression and role of a particular family of cell-cell adhesion molecules, the cadherins, during early brain morphogenesis in vertebrates.
Cadherins are cell surface glycoproteins, which mediate cell-cell adhesion by a Ca2+- dependent mechanism. Results from in vitro studies with cadherin-transfected cell lines show that cadherins preferentially bind to each other in a homophilic fashion. In the developing vertebrate brain, at least two dozen cadherins are expressed (reviewed in Redies, 1995, 2000).
We have shown that several cadherins are expressed in a restricted fashion by particular developing brain nuclei and neural circuits in the embryonic chicken and mouse brain (Redies et al., 1992, 1993, 2000, 2001; Redies and Takeichi, 1993a; Arndt and Redies, 1996; Fushimi et al., 1997; Korematsu and Redies, 1997a, 1997b; Yoon et al., 2000). Moreover, many cadherins are expressed in a segmental ("neuromeric") fashion in the early chicken and mouse forebrain (Gänzler and Redies, 1995; Korematsu and Redies, 1997a; Fushimi et al., 1997). These results suggest that cadherins and other adhesion molecules might regulate developmental processes involved in the transformation from the neuromeric organization of the early neuroepithelium to the anatomy of the mature brain. Specifically, we propose that cadherins regulate the formation of brain nuclei, fiber tracts and neural circuits by mediating the sorting and aggregation of early neurons and neurites in the embryonic vertebrate brain (reviewed in Redies, 1995; 2000; Hirano et al., 2003). The formation and specificity of neural circuitry may be mediated by cadherins also at the synaptic level (reviewed in Hirano et al., 2003).
Cadherin expression in the visual system and cerebellar system was studied in greater detail. In the cerebellum, each cadherin is expressed in restricted parasagittal domains (Arndt and Redies, 1996; Fushimi et al., 1997; Korematsu et al., 1997b; Arndt et al., 1998; Arndt and Redies, 1998). By studying multiple cadherins, a parasagittal pattern of adhesive segments consisting of Purkinje cell clusters was found. In this pattern, the segments are separated by thin ribbons/raphé of early migrating neurons (Arndt et al., 1998). In the visual system, different subpopulations of neuronal cell types express different cadherins. For example, a subset of ganglion cells expresses cadherin-6B and cadherin-7. Their axons project to specific visual nuclei of the diencephalon some of which express the same cadherins in a matching fashion (Wöhrn et al., 1998a; Becker and Redies, 2003). The layers of the visual tectum also differentially express cadherins. In the deeper tectal layers, the projection neurons express particular combinations of cadherins. As the axons of these neurons leave the tectum, they fasciculate according to which combination of cadherins they express, and the different cadherin-positive fascicles then take separate paths to their different target areas in other parts of the brain (Wöhrn et al., 1999). The ectopic expression of cadherins by the tectofugal fibers causes them to join those fiber pathways that express the same cadherin, as shown by in ovo elecotroporation (Treubert-Zimmermann et al., 2002).
Currently, we are studying the role of cadherins in brain development by in vivo (in ovo) electroporation. This technique allows the genetic manipulation of cadherin expression at a regional level in the living brain. We have already shown that the forced overexpression of cadherins plays a role in axon pathfinding (Treubert-Zimmermann et al., 2002) and in the migration of Purkinje cell precursor cells in the developing cerebellum (Luo et al., 2004). Further studies are currently being carried out in our group to demonstrate the diverse roles of cadherins in vertebrate brain development.
Supported by DFG (RE616/4-4)
Cadherins are cell surface glycoproteins, which mediate cell-cell adhesion by a Ca2+- dependent mechanism. Results from in vitro studies with cadherin-transfected cell lines show that cadherins preferentially bind to each other in a homophilic fashion. In the developing vertebrate brain, at least two dozen cadherins are expressed (reviewed in Redies, 1995, 2000).
We have shown that several cadherins are expressed in a restricted fashion by particular developing brain nuclei and neural circuits in the embryonic chicken and mouse brain (Redies et al., 1992, 1993, 2000, 2001; Redies and Takeichi, 1993a; Arndt and Redies, 1996; Fushimi et al., 1997; Korematsu and Redies, 1997a, 1997b; Yoon et al., 2000). Moreover, many cadherins are expressed in a segmental ("neuromeric") fashion in the early chicken and mouse forebrain (Gänzler and Redies, 1995; Korematsu and Redies, 1997a; Fushimi et al., 1997). These results suggest that cadherins and other adhesion molecules might regulate developmental processes involved in the transformation from the neuromeric organization of the early neuroepithelium to the anatomy of the mature brain. Specifically, we propose that cadherins regulate the formation of brain nuclei, fiber tracts and neural circuits by mediating the sorting and aggregation of early neurons and neurites in the embryonic vertebrate brain (reviewed in Redies, 1995; 2000; Hirano et al., 2003). The formation and specificity of neural circuitry may be mediated by cadherins also at the synaptic level (reviewed in Hirano et al., 2003).
Cadherin expression in the visual system and cerebellar system was studied in greater detail. In the cerebellum, each cadherin is expressed in restricted parasagittal domains (Arndt and Redies, 1996; Fushimi et al., 1997; Korematsu et al., 1997b; Arndt et al., 1998; Arndt and Redies, 1998). By studying multiple cadherins, a parasagittal pattern of adhesive segments consisting of Purkinje cell clusters was found. In this pattern, the segments are separated by thin ribbons/raphé of early migrating neurons (Arndt et al., 1998). In the visual system, different subpopulations of neuronal cell types express different cadherins. For example, a subset of ganglion cells expresses cadherin-6B and cadherin-7. Their axons project to specific visual nuclei of the diencephalon some of which express the same cadherins in a matching fashion (Wöhrn et al., 1998a; Becker and Redies, 2003). The layers of the visual tectum also differentially express cadherins. In the deeper tectal layers, the projection neurons express particular combinations of cadherins. As the axons of these neurons leave the tectum, they fasciculate according to which combination of cadherins they express, and the different cadherin-positive fascicles then take separate paths to their different target areas in other parts of the brain (Wöhrn et al., 1999). The ectopic expression of cadherins by the tectofugal fibers causes them to join those fiber pathways that express the same cadherin, as shown by in ovo elecotroporation (Treubert-Zimmermann et al., 2002).
Currently, we are studying the role of cadherins in brain development by in vivo (in ovo) electroporation. This technique allows the genetic manipulation of cadherin expression at a regional level in the living brain. We have already shown that the forced overexpression of cadherins plays a role in axon pathfinding (Treubert-Zimmermann et al., 2002) and in the migration of Purkinje cell precursor cells in the developing cerebellum (Luo et al., 2004). Further studies are currently being carried out in our group to demonstrate the diverse roles of cadherins in vertebrate brain development.
Supported by DFG (RE616/4-4)
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