Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

NRH1 and Wnt signaling come together in convergent extension

20.07.2004


The African clawed frog, Xenopus laevis, begins development as a compact ball of cells that undergoes a dramatic transformation through cell migrations and positional rearrangements that result in the separation of the embryo into three distinct germ layers, which go on to give rise to all of the tissues and structures in the adult animal’s body. During this transformation, known as gastrulation, the embryo changes from a roughly spherical shape to an elongated, streamlined form through a process called convergent extension (CE), in which polarized cells migrate to and merge at the embryo’s midline, driving it to lengthen along its anterior-posterior axis.



A number of genes involved in the regulation of convergent extension have been identified in amphibians and other vertebrates, such as zebrafish, but the picture of the underlying molecular mechanisms remains incomplete. Researchers at the RIKEN Center for Developmental Biology (CDB; Kobe, Japan) have now added a new piece to the puzzle. In a report published in the advanced online edition of Nature Cell Biology, Noriaki Sasai and colleagues in the Laboratory for Organogenesis and Neurogenesis (Group Director, Yoshiaki Sasai) show that the product of the gene NRH1 is essential to the regulation of CE movements in the frog.

While performing a screen of genes expressed in the posterior neuroectoderm, Sasai et al. identified a gene encoding a protein that showed similarities to p75NTR, a neurotrophin receptor. (Neurotrophins are molecules that function in the survival, growth and migration of neurons.) However, on testing its affinity for neurotrophin ligands, the group found that, unlike p75NTR, NRH1 did not bind with neurotrophins, which led them to seek other biological roles for the protein.


Experiments in which NRH1 was overexpressed by injecting its messenger RNA directly into very early (4-cell stage) embryos resulted in shortening of the body axis and the failure of mesodermal and neural plate marker gene expression to converge on the midline or extend axially. Interestingly, interfering with NRH1 function by introducing morpholinos to block production of the NRH1 protein had similar effects – the inhibition of convergent extension. That both gain and loss of NRH1 function resulted in the failure of CE activity suggested that the gene’s function in this process is tightly regulated.

These first findings led Sasai to investigate possible interactions between NRH1 and genes involved in the Wnt/PCP (planar cell polarity) signaling pathway, which is also known to play an important role in the regulation of CE movements in both fish and frog through the activity of downstream small GTPases. This protein family, which includes Rho, Rac and Cdc42, interacts with the cytoskeleton and plays important roles in the dynamics of cell morphology and motility. Overexpression and loss-of-function of NRH1 in the marginal zone (where convergent extension originates) respectively resulted in increased and decreased Rho, Rac and Cdc42 activity, confirming the link between NRH1 and Rho-family small GTPases. Loss of NRH1 function could be rescued by the co-injection of Frz7, a Wnt receptor functioning upstream of Rho, Rac and Cdc42 in the PCP pathway and, similarly, NRH1 complemented a dominant-negative Frz7 phenotype, indicating the two proteins play compensatory and mutually independent roles in the activation of small GTPases.

Further experiments showed that NRH1’s effects on CE movements are also mediated by a second branch of the Wnt/PCP pathway, in which MKK7 and JNK work to phosphorylate c-Jun in the animal cap (a region of prospective ectoderm located on the roof of the blastocoel, a hollow in the spherical early embryo). As with the small GTPases, the activation of the MKK7-JNK cascade could also be effected by either Frz7 or NRH1, but it was found that NRH1 functioned independently of Xdsh, another upstream regulator of Rho-family small GTPase activity in the Wnt/PCP pathway. The transduction mechanisms by which NRH1 interacts with Wnt/PCP signaling factors remain to be worked out, as do the specifics of the inter-related but apparently independent roles of NRH1 and PCP signaling in the control of cell movements within the developing embryo.

Doug Sipp | EurekAlert!
Further information:
http://www.cdb.riken.jp

More articles from Life Sciences:

nachricht Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>