Multiple Roles of Wnt signaling pathway in the body

In recent years, scientists have found that the WNT signaling pathway plays a variety of key roles in the body.

[1] Cell: Wnt signaling pathway mediates neuronal to intestinal cell mitochondrial stress response

Mitochondria are not only the center of cellular energy supply, but also one of the important organelles that regulate the aging process and affect neurodegenerative diseases. When the mitochondrial function is damaged, the mitochondrial unfolded protein reaction (UPRmt) will be initiated, and the expression levels of mitochondrial molecular chaperones, proteases, and metabolism-related genes will be up-regulated, and the mitochondrial homeostasis will be reconstructed. In a multicellular body, different tissues (neural cells - intestinal cells) also sense and coordinate their respective mitochondrial unfolded protein responses, ultimately and systemically regulating the body's overall metabolic level and affecting the aging process. However, it is unclear how the organizations regulate and coordinate the regulation mechanisms of their mitochondrial homeostasis.
On July 26, the Tian Hao Research Group of the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences collaborated with Andrew Dillin, a professor at the University of California, Berkeley, and published an article entitled “Mitochondrial unfolded protein response is mediated cell-non-autonomously by retromer-dependent Wnt signaling” on Cell. The study found that Wnt, an important factor in developmental regulation, is involved in mediating mitochondrial stress responses between nerve cells and intestinal cells. It is also revealed that this transcellular and inter-tissue regulation of mitochondrial stress response is dependent on the Retromer complex, the Wnt signaling pathway, and the neurotransmitter serotonin.

[2] Science: New research to solve the mystery of Wnt signal specificity

In a new study, under the leadership of Benoit Vanhollebeke, a researcher at the Free University of Brussels in Belgium, the researchers solved an important cell signaling mystery associated with Wnt signaling specificity. The relevant research results were published online in the journal Science on July 19, 2018.
Wnt is an ancient signaling pathway whose evolution seems to be traceable to the emergence of multicellular animals. It plays a key role in intercellular communication and controls several aspects of embryonic development and tissue homeostasis. When dysfunctional, Wnt signaling may be the origin of many diseases, especially several types of cancer. Given that this signaling pathway has 10 receptors and 19 ligands, and these receptors and ligands recognize each other, the complexity of this signaling pathway appears to be dazzling. How do vertebrate cells try to explain the many Wnt signals they encounter and trigger a sufficiently strong response? This interpretation mechanism is exactly what these researchers have just discovered.

[3] Cell: Synchronized Wnt and Notch pulse control embryo segmentation

In the process of embryos forming complex organisms from a single cell, a large number of structural processes ensure that the right cells develop in the right place and at the right time. Cells activate specific genes in a rhythmic manner during this early development, causing the activation waves to sweep the entire embryo.
Now, in a new study, the Alexander Aulehla lab and the Christoph Merten lab from the European Molecular Biology Laboratory (EMBL) confirmed that the timing between the two sets of specific waves controlled by the Wnt and Notch pathways can lead to embryos to form a new segment.
The formation of new segments in mouse embryos is controlled by molecular clocks. The two key signaling pathways in this process are called Wnt signaling pathway and Notch signaling pathway. These two pathways exhibit periodic active pulses that occur at the same rate as the segmentation. Today, these researchers have confirmed that the timing between these two waves leads to embryonic segmentation. At a particular point in time, the Wnt and Notch waves will stay in sync and overlap, which corresponds to the new segmentation.

[4] Diabetes: The canonical Wnt signaling pathway factor TCF7L2 regulates adipocyte development and function

Many previous studies have shown that the gene encoding Wnt signaling pathway transcription factor TCF7L2 is a very strong candidate for type 2 diabetes, but how this factor is involved in the development of type 2 diabetes has not been well understood. TCF7L2 protein is a key transcriptional effector of Wnt/β-catenin signaling pathway. Wnt/β-catenin signaling pathway can play a very important regulatory role in development. For the lipogenesis process, previous studies have shown that this signaling pathway plays a negative regulation role. However, the effect of TCF7L2 on the development and function of fat cells is still unclear.
In a recent study, researchers from the University of Texas Health Science Center in the international academic journal Diabetes presented their latest advances in TCF7L2 in adipocyte development and function. The researchers first found in vitro that the expression of TCF7L2 protein was gradually increased during the differentiation of 3T3L1 and primary adipose precursor cells, and the expression of TCF7L2 was required for the regulation of Wnt signaling on adipogenesis.

[5] ASCO2016: Wnt signaling pathway plays an important role in the pathogenesis of young patients with colorectal cancer

While increasing screening continues to reduce the overall incidence of colorectal cancer, the incidence of colorectal cancer patients under 50 years of age has been increasing, and colorectal cancer is becoming a common malignant disease in younger patients. Recently, researchers from the University of Colorado, School of Medicine, have revealed a possible cause of increased risk of colorectal cancer in young patients. There are often many identical genetic changes in young and elderly patients, while young patients are more prone to genetic changes, such as changes in the Wnt signaling pathway, which can drive the survival, growth and proliferation of cancer stem cells.
Researcher Dr. Christopher Lieu said that genes associated with the Wnt signaling pathway are more prone to frequent mutations in young colorectal cancer patients. We analyzed the genetic characteristics of 4,699 colorectal cancer tissue samples in the study. Although the cancer tissues of young and old patients share the same genetic changes, the CTNNB1 and FAM123B genes in younger patients are more susceptible to alteration, and these genes play an important role in the Wnt signaling pathway.

[6] Cell Rep: An important signaling molecule for cell reprogramming - WNT protein

Recently, in a research paper published in the international magazine Cell Reports, researchers from the University of California discovered a signal molecule that is critical for cell reprogramming in the study of rare genetic diseases. The study was developed for stem cell-based signaling. Regenerative medicine therapy has brought new ideas and hopes for tissue damage repair and cancer treatment.
In the article, researcher Karl Willert and his colleagues developed a new model for the treatment of focal skin hypoplasia (FDH) using induced pluripotent stem cells (ipsC), a rare disease caused by mutations in the PORCN gene. The main features of the disease are skin deformities, such as thin skin stripes or different shapes and visible vein clustering.
In the article, the researchers found that when WNT protein is added, FDH fibroblasts or skin cells can be successfully reprogrammed into induced pluripotent stem cells. WNT protein is a conserved signaling molecule that can be regulated during embryonic development and intercellular interactions.