Signaling factors known as Wnts play an integral role in processes relating to body pattern formation during embryonic development. The Wnts can trigger a broad range of different signaling pathways; the specification of which particular pathway gets activated is managed by additional interactions between Wnt receptors and specific cofactors.
One process controlled by the Wnts is the planar cell polarity (PCP) pathway, which is essential to proper epithelial formation, the cells that line the surface of the skin and body cavities. “Each cell in epithelium has a polarity in the plane of the epithelial sheet—this can be easily seen in the fact that hairs are aligned in one direction,” explains Hiroshi Sasaki of the RIKEN Center for Developmental Biology in Kobe. “The PCP pathway regulates such polarity of cells.”
Sasaki’s group has been searching for novel genes involved in body pattern formation, and recently identified Cthrc1, a gene that exhibits spatial and temporal expression patterns that mirror those of known components of the PCP pathway. This led them to hypothesize that Cthrc1 may also be acting within this signaling cascade.
In order to test this model, they generated strains of mice in which the expression of Cthrc1 had been eliminated1. Disruption of this gene had no apparent effect on its own, but when Sasaki’s team further modified the mouse strain to reduce expression of the PCP signaling gene Vangl2, they observed marked abnormalities in orientation and alignment of the sensory hair cells of the inner ear. Reduction of Vangl2 alone was not sufficient to cause these defects, further supporting a role for Cthrc1 in PCP.
Subsequent analysis showed that the Cthrc1 protein directly interacts with and stabilizes the complex formed by Wnts with their receptors and PCP-related co-receptors, and thereby specifically enhances PCP pathway activation while suppressing other Wnt-mediated signaling cascades. Importantly, this interaction occurs outside the cell. “Our paper reports—for the first time—an extracellular molecule involved in pathway selection by Wnt signaling molecules,” says Sasaki, “and therefore reveals a novel mechanism for pathway selection.”
Beyond these insights, however, this work also yields a new mystery—if eliminating Cthrc1 expression causes no ill effects, which protein is taking its place? “Because there are no Cthrc1-related genes in the mouse genome, structurally unrelated molecules must play similar roles in Wnt signaling,” says Sasaki. “We think that it is necessary to identify such molecules to reveal the importance of this mechanism in Wnt signaling.”
1. Yamamoto, S., Nishimura, O., Misaki, K., Nishita, M., Minami, Y., Yonemura, S., Tarui, H. & Sasaki, H. Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Developmental Cell 15, 23–26 (2008).
The corresponding author for this highlight is based at the RIKEN Laboratory for Embryonic Induction
Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
Foods of the future
15.08.2018 | Georg-August-Universität Göttingen
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
21.08.2018 | Ecology, The Environment and Conservation
21.08.2018 | Life Sciences
21.08.2018 | Power and Electrical Engineering