Planar cell polarity genes and neural tube closure

Abstract

Closure of the neural tube is essential for normal development of the brain and spinal cord. Failure of closure results in neural tube defects (NTDs), common and clinically severe congenital malformations whose molecular mechanisms remain poorly understood. On the other hand, it is increasingly well established that common molecular mechanisms are employed to regulate morphogenesis of multicellular organisms. For example, signaling triggered by polypeptide growth factors is highly conserved among species and utilized in multiple developmental processes. Recent studies have revealed that the Drosophila planar cell polarity (PCP) pathway, which directs position and direction of wing hairs on the surface of the fly wing, is well conserved, and orthologs of several genes encoding components of the pathway are also found in vertebrates. Interestingly, in vertebrates, this signaling pathway appears to be co-opted to regulate "convergent extension" cell movements during gastrulation. Disruption of vertebrate PCP genes in Xenopus laevis or zebrafish causes severe gastrulation defects or the shortening of the trunk, as well as mediolateral expansion of somites. In Xenopus, in which the neural tube closes by elevation and fusion of neural folds, inhibition of convergent extension can also prevent neural tube closure causing a "spina bifida-like" appearance. Furthermore, several of the genes involved in the PCP pathway have recently been shown to be required for neural tube closure in the mouse, since mutation of these genes causes NTDs. Therefore, understanding the mechanisms underlying the establishment of cell polarity in Drosophila may provide important clues to the molecular basis of NTDs.

Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm

“…Similar to our observations on presomitic mesoderm, the motility of chemokine-guided germ cells in zebrafish requires cadherins and the non-canonical planar polarity genes RhoA and Rac1 GTPases (Ueno and Greene, 2003;Kardash et al, 2010). In zebrafish, Wnt11 via Disheveled signals RhoA and Rho kinase to mediate convergence and extension (Marlow et al, 2002;Solnica-Krezel and Eaton, 2003).…”

“…RhoA kinase 2 concentrates in the posterior of polarized zebrafish cells during convergence and extension where it could medicate adhesion (Yin et al, 2008). At the same time Rac1 mediates convergence extensions downstream of Strabismus via Prickle (Ueno and Greene, 2003) and is more concentrated at the anterior of cells (Yin et al, 2008), where it could activate actin polymerization and thus lamellipodia formation. In Xenopus, Cdc42 is also required for polarized convergent extension and may work downstream of the non-canonical Wnt5a, via PKC-a (Choi and Han, 2002).…”

Essential role of non-canonical Wnt signalling in neural crest migration

“…In recent years, evidence has accumulated from studies in zebrafish and Xenopus embryos that supports the notion that the migration of mesodermal cells during gastrulation is dependent on factors similar to those involved in planar cell polarity (PCP) in Drosophila, which are activated by non-canonical Wnt signalling (for reviews, see Keller, 2002;Mlodzik, 2002;Myers et al, 2002;Ueno and Greene, 2003;Veeman et al, 2003b;Wallingford et al, 2002).…”

Comparative analysis of neurulation: First impressions do not count

“…Prior to the onset of primary neurulation, the neural plate narrows, a process that involves cell elongation and oriented cell division (Colas and Schoenwolf, 2001) and is regulated in part by the noncanonical Wnt-signaling pathway (also known as the planar cell polarity/PCP pathway; Ueno and Greene, 2003;Zohn et al, 2003;Copp, 2005;Doudney and Stanier, 2005;Wang and Nathans, 2007). Following narrowing, the neural plate bends into a tube, while maintaining rigid cell-cell contacts.…”

“…This pathway is generally thought to narrow and elongate the neural plate prior to the onset of neurulation. In amphibians, PCP signaling controls polarized cell movements in the neural plate, prior to the onset of neurulation Ueno and Greene, 2003;Zohn et al, 2003;Wang and Nathans, 2007). In amniotes, in which neural plate cells do not exhibit mesenchymal characteristics (and are thus unlikely to be migratory), this pathway may regulate other processes, such as the orientation of cell division (Sausedo et al, 1997;Wallingford, 2005;Wang et al, 2006;Wang and Nathans, 2007).…”