FAK-mediated extracellular signals are essential for interkinetic nuclear migration and planar divisions in the neuroepithelium

Introduction During the morphogenesis of the neural tube, neural progenitors continuously divide, and post mitotic neurons then migrate to form complex neural networks. It is widely conserved among vertebrates that this mitotic process takes place near the lumen, the apical side of the neural tube (Gotz and Huttner, 2005). When viewed at the cellular level, this apically localized mitosis is the region of output for the cell-cycle-dependent oscillation of the nuclei within the neuroepithelium. Mitotic (M phase) nuclei are located in close proximity to the apical surfaces, whereas nuclei undergoing DNA synthesis (S phase) are displaced more basally. This characteristic movement of nuclei is known as interkinetic nuclear migration (INM) (Fujita, 1964; Sauer, 1935) and is thought to be important for maintaining a neural progenitor pool during neurogenesis (Baye and Link, 2007; Del Bene et al., 2008; Murciano et al., 2002; Xie et al., 2007). Furthermore, planar cell divisions near the apical surface are thought to be important to maintain the progenitor pool (Gotz and Huttner, 2005). Indeed, recent works suggest that most divisions during both proliferative and neurogenic stages are planar (that is, parallel to the apical surface), whereas vertical or oblique divisions are rarely seen, and daughter cells that inherit both the apical and basal components are suggested to remain in the progenitor pool (Konno et al., 2008). Although INM and planar cell divisions have been regarded as hallmarks of vertebrate neural progenitors, their cellular and molecular mechanisms are just beginning to be elucidated. Previous studies have suggested the involvement of several intracellular components such as the actin and microtubule cytoskeletons, molecules involved in adherens junctions, polarity complex and the centrosome (Cappello et al., 2006; Imai et al., 2006; Lien et al., 2006; Murciano et al., 2002; Siller and Doe, 2009; Xie et al., 2007). However, it remains unclear whether extracellular molecules, such as components of the extracellular matrix (ECM), have any role in INM and mitotic orientation of neural progenitors, and if so, how they interact with the intracellular machinery that drives this process. Indeed, the ECM has long been shown to participate in neurogenesis (see below), but there are no reports of vertebrate ECM mutants with defective INM and mitotic orientation. In this context, the medaka mutant tacobo (tab) used in the present study provides a unique framework. The medaka fish, Oryzias latipes, is an emerging vertebrate model and now has a high quality draft genome and a FAK-mediated extracellular signals are essential for interkinetic nuclear migration and planar divisions in the neuroepithelium