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Unformatted text preview: INTRODUCTION Cadherins constitute a family of Ca 2+-dependent cell adhesion molecules crucial for several steps during embryonic development. N-cadherin (cadherin 2, Ncad) belongs to the subfamily of classical cadherins characterized by five extracellular cadherin-binding domains separated by Ca 2+- binding pockets, a transmembrane domain and an intracellular β-catenin-binding domain (for a review, see Tepass et al., 2000). It was discovered as the first of about 30 cadherins expressed in the vertebrate embryonic or adult nervous system (Hatta and Takeichi, 1986; Miyatani et al., 1989; Redies, 2000; Yagi and Takeichi, 2000). Ncad expression is relatively ubiquitous during early vertebrate development, but later becomes restricted to particular sets of nuclei and neuronal layers within the central nervous system (CNS) (Redies et al., 1993; Redies and Takeichi, 1993). Ncad mRNA is also expressed in the eyes, in various ganglia of the peripheral nervous system, and in the developing heart and somites. Most evidence regarding Ncad function has been gathered from cell culture experiments. Forced expression of Ncad causes increased migration, invasiveness and metastatic activity in breast cancer cell lines (Hazan et al., 2000; Nieman et al., 1999). Accordingly, upregulation of Ncad expression accompanied by loss of E-cadherin mRNA is potentially a key event in the epithelial-mesenchymal transitions associated with the metastatic phenotype during cancer progression (Tran et al., 1999). Moreover, ectopic expression of Ncad is also reported to induce scattering and epithelial-mesenchymal transition in squamous carcinoma cells (Islam et al., 1996), as well as reduced adhesion and increased migration in oligodendrocyte cultures on astrocyte monolayers (Schnadelbach et al., 2000). In contrast to these results, increased attachment and reduced motility has been observed following overexpression of Ncad in murine sarcoma cells (Dufour et al., 1999). These apparently contradicting results demonstrate that Ncad may regulate cell adhesion and migration in a tissue- and context-specific manner. 3281 Development 129, 3281-3294 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV1825 N-cadherin (Ncad) is a classical cadherin that is implicated in several aspects of vertebrate embryonic development, including somitogenesis, heart morphogenesis, neural tube formation and establishment of left-right asymmetry. However, genetic in vivo analyses of its role during neural development have been rather limited. We report the isolation and characterization of the zebrafish parachute ( pac ) mutations. By mapping and candidate gene analysis, we demonstrate that pac corresponds to a zebrafish n- cadherin ( ncad ) homolog. Three mutant alleles were sequenced and each is likely to encode a non-functional Ncad protein. All result in a similar neural tube phenotype that is most prominent in the midbrain, hindbrain and the posterior spinal cord. Neuroectodermal cell adhesion isposterior spinal cord....
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This note was uploaded on 05/28/2010 for the course BIOLOGY 03234 taught by Professor Sochacka during the Spring '10 term at Ghent University.
- Spring '10