Planar Cell Polarity Links Axes of Spatial Dynamics in Neural-Tube Closure

Abstract

Neural-tube closure is a critical step of embryogenesis, and its failure causes serious birth defects. Coordination of two morphogenetic processes--convergent extension and neural-plate apical constriction--ensures the complete closure of the neural tube. We now provide evidence that planar cell polarity (PCP) signaling directly links these two processes. In the bending neural plates, we find that a PCP-regulating cadherin, Celsr1, is concentrated in adherens junctions (AJs) oriented toward the mediolateral axes of the plates. At these AJs, Celsr1 cooperates with Dishevelled, DAAM1, and the PDZ-RhoGEF to upregulate Rho kinase, causing their actomyosin-dependent contraction in a planar-polarized manner. This planar-polarized contraction promotes simultaneous apical constriction and midline convergence of neuroepithelial cells. Together our findings demonstrate that PCP signals confer anisotropic contractility on the AJs, producing cellular forces that promote the polarized bending of the neural plate.

Apical constriction: themes and variations on a cellular mechanism driving morphogenesis

“…In addition, RhoA can activate Diaphanous (Dia)-related formins, which nucleate and facilitate the assembly of unbranched actin filaments (Goode and Eck, 2007). Apical constriction in several vertebrate and invertebrate systems requires RhoA GTPase activation (Barrett et al, 1997;Hacker and Perrimon, 1998;Plageman et al, 2011;Nishimura et al, 2012). In Drosophila gastrulation, RhoA (Rho1 in Drosophila) activation plays a central role in a signaling pathway that links tissue patterning and cell fate to apical constriction and cell invagination (Leptin, 2005).…”

Nodal and FGF coordinate ascidian neural tube morphogenesis

“…However, there are also differences. For example, Flamingo (Celsr) and Prickle regulate intercalary behavior through the planar cell polarity pathway (Nishimura et al, 2012;Takeuchi et al, 2003), but are absent in the floor plate. Curiously, these genes are expressed in the lateral neural plate, which undergoes stacking rather than convergence (Mita et al, 2010;Noda and Satoh, 2008).…”

Cell Chirality Induces Collective Cell Migration in Epithelial Sheets

“…The relatively high concentration of myosin generates strong contraction, which shrinks the cell boundaries, and the cells undergo autonomous intercalation along the dorsal-ventral axis [9,12]. The polarized contraction also plays an important role in the bending of cell sheets [13,14].…”

“…δ ij is the Kronecker delta. Experimental observations also show thatγ ij depends on the orientation of the cell boundary ij [9,13,21]. Since the characteristic time for myosin to relocate (several tens of seconds) is much shorter than that of cell configuration change (several tens of minutes), we set upγ ij to be a given functionγ of the angle θ ij between the cell boundary ij and the x axis at the time t, i.e.,γ ij ðtÞ ≃γ(θ ij ðtÞ): ð6Þ…”