Cdh2 coordinates Myosin-II dependent internalisation of the zebrafish neural plate

Abstract

Tissue internalisation is a key morphogenetic mechanism by which embryonic tissues generate complex internal organs and a number of studies of epithelia have outlined a general view of tissue internalisation. Here we have used quantitative live imaging and mutant analysis to determine whether similar mechanisms are responsible for internalisation in a tissue that apparently does not have a typical epithelial organisation – the zebrafish neural plate. We found that although zebrafish embryos begin neurulation without a conventional epithelium, medially located neural plate cells adopt strategies typical of epithelia in order to constrict their dorsal surface membrane during cell internalisation. Furthermore, we show that Myosin-II activity is a significant driver of this transient cell remodeling which also depends on Cdh2 (N-cadherin). Abrogation of Cdh2 results in defective Myosin-II distribution, mislocalised internalisation events and defective neural plate morphogenesis. Our work suggests Cdh2 coordinates Myosin-II dependent internalisation of the zebrafish neural plate.

Hingepoints and neural folds reveal conserved features of primary neurulation in the zebrafish forebrain

“…Hingepoints are restricted to the ANP in zebrafish, however they are also present in more posterior regions in amniotes. Despite this difference, individual cells in the medial zone of the hindbrain neural plate were recently shown to internalize via a myosin-dependent mechanism 46 . Such variation from the organized cell clusters forming hingepoints in the zebrafish forebrain could be explained by precocious epithelialization of the ANP 37 .…”

Mechanisms of vertebrate neural plate internalization

“…In amniote embryos including mammals and birds, the neural plate is a single polarized epithelium with well-defined apical junctional components at the most apical surface while underlain by extracellular matrix at the most basal side (Schoenwolf and Franks, 1984). In anamniote embryos on the other hand, the organization of the neural plate is more variable and can be a single-layered epithelial structure as in newts (Brun and Garson, 1983), a bi-layered epithelium like in frogs (Schroeder, 1970), or a rather more complex layered structure with hybid features of both immature epithelium and mesenchyme as in teleost fish (Clarke, 2009;Araya et al, 2019). Although these early differences in cell and tissue cyto-architecture are commonly thought to influence subsequent steps of neurulation (i.e.…”

“…Although these early differences in cell and tissue cyto-architecture are commonly thought to influence subsequent steps of neurulation (i.e. dorsal folding, where the central canal is directly formed by an inward movement of a sheet of cells versus cavitation, where the central canal is only generated after the formation of a transient solid structure with no lumen), evidence shows that initial stages of neural plate morphogenesis are characterized by a series of common collective cell remodeling events at the developing dorsal midline (Colas and Schoenwolf, 2001;Wallingford and Harland, 2002;Williams et al, 2014;Butler and Wallingford, 2018;Araya et al, 2019). Moreover, while neural tube formation has been shown to be influenced by the interaction with adjacent tissues (Morita et al, 2012;Araya et al, 2014) and molecular cues (Ybot-Gonzalez et al, 2002;Araya et al, 2015), isolated tissue explants (Elul et al, 1997;Keller et al, 1992) as well as quantitative live imaging studies (Rolo et al, 2009;Nishimura et al, 2012;Galea et al, 2017) support the notion that early neural plate shaping depends largely on the activities of neural cells themselves.…”

“…1A). While other embryos such as teleost fish form a neural tube in the absence of an obvious morphological neural groove, midline tissue constriction is still a key step that initiates an organized transient multicellular neural keel structure (Araya et al, 2019). At the cell level, tissue internalization is chiefly achieved by apical cell surface reduction followed by the concomitant elongation along its apical-basal axis as cells deepen into the tissue (Sawyer et al, 2010;Martin and Goldstein, 2014).…”

“…However, it is clear that mechanical coupling between adjacent cells appears as key regulators of collective midline cell-cell morphogenesis (Morita et al, 2010;Hong and Brewster, 2006). During neurulation, the expression of classical type-I cadherin member N-cadherin has been indicated to play a major role in mechanical coupling during early neural plate development (Radice et al, 1997;Hong and Brewster, 2006;Nandadasa et al, 2009;Morita et al, 2010;Araya et al, 2019). However, how cell-cell adhesion systems integrate and transmit both biochemical and biomechanical information during neural plate internalization is not well understood.…”