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 Cell Division at High Speed
19.06.2019 | Julius-Maximilians-Universität Würzburg

nachricht Monitoring biodiversity with sound: how machines can enrich our knowledge
18.06.2019 | Georg-August-Universität Göttingen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Successfully Tested in Praxis: Bidirectional Sensor Technology Optimizes Laser Material Deposition

The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.

Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

Im Focus: Tube anemone has the largest animal mitochondrial genome ever sequenced

Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.

The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

A new force for optical tweezers awakens

19.06.2019 | Physics and Astronomy

New AI system manages road infrastructure via Google Street View

19.06.2019 | Information Technology

A new manufacturing process for aluminum alloys

19.06.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>