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 New type of photosynthesis discovered
17.06.2018 | Imperial College London

nachricht New ID pictures of conducting polymers discover a surprise ABBA fan
17.06.2018 | University of Warwick

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

Im Focus: Water is not the same as water

Water molecules exist in two different forms with almost identical physical properties. For the first time, researchers have succeeded in separating the two forms to show that they can exhibit different chemical reactivities. These results were reported by researchers from the University of Basel and their colleagues in Hamburg in the scientific journal Nature Communications.

From a chemical perspective, water is a molecule in which a single oxygen atom is linked to two hydrogen atoms. It is less well known that water exists in two...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

A sprinkle of platinum nanoparticles onto graphene makes brain probes more sensitive

15.06.2018 | Materials Sciences

100 % Organic Farming in Bhutan – a Realistic Target?

15.06.2018 | Ecology, The Environment and Conservation

Perovskite-silicon solar cell research collaboration hits 25.2% efficiency

15.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>