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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>