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 Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo

nachricht Full of hot air and proud of it
18.04.2018 | University of Pittsburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Diamond-like carbon is formed differently to what was believed -- machine learning enables development of new model

19.04.2018 | Materials Sciences

Electromagnetic wizardry: Wireless power transfer enhanced by backward signal

19.04.2018 | Physics and Astronomy

Ultrafast electron oscillation and dephasing monitored by attosecond light source

19.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>