Wnt Meaning: The Wnt Signaling Pathway and Its Function
The Wnt signaling pathway is a critical cell communication network that governs organism development and shifts to manage tissue maintenance throughout adult life.
Wnt refers to a family of secreted proteins that facilitate communication between cells in virtually all animal species. The name “Wnt” combines “Wingless,” a gene from the fruit fly Drosophila, and “Int-1,” a proto-oncogene from mice. This fusion reflects the discovery that these genes were homologous, revealing a highly conserved signaling system. The Wnt signaling pathway is a process initiated by these proteins that controls cell behavior.
The Wnt Signaling Mechanism
The Wnt signaling process begins when a cell releases a Wnt protein. This protein travels a short distance and binds to a specific “Frizzled” family receptor on a target cell’s surface, much like a key fitting into a lock. This binding initiates an internal cascade that alters which genes are turned on or off in the receiving cell.
There are two primary branches of this pathway. The most studied is the canonical pathway, which involves a protein called β-catenin. In the absence of a Wnt signal, β-catenin is constantly destroyed, but when a Wnt protein binds to its receptor, this destruction is halted. As β-catenin accumulates, it travels into the cell’s nucleus and partners with other proteins to activate specific genes.
The other branches are the non-canonical pathways, which do not rely on β-catenin. One such pathway, the planar cell polarity pathway, helps organize the cell’s internal skeleton, affecting its shape and movement. Another, the Wnt/calcium pathway, regulates calcium levels within the cell, which can influence different cellular processes.
Role in Embryonic Development
During embryonic development, Wnt signaling directs cells to form a complete organism. It is active from the earliest stages, helping to establish the body plan by defining the head-to-tail and back-to-belly axes. This process ensures that body parts form in their correct locations.
The pathway is also involved in organ formation, with the development of the heart, kidneys, and lungs depending on Wnt signals. These signals instruct cells to differentiate into specialized types and also guide the formation of limbs.
Wnt signaling achieves this by controlling cell proliferation (cell growth and division) and cell fate specification, which determines what a young cell will become. Through its influence on gene expression, the pathway provides the information cells need to build tissues and organs. Impairment of these signals during development can lead to congenital defects.
Function in Adult Tissues
After an organism is fully formed, Wnt signaling transitions to a role of maintenance and repair. In adult tissues, its activity is restricted to areas with stem cells, which regenerate tissues that undergo constant wear. The pathway promotes the self-renewal of these stem cells, ensuring a supply of new cells to replace old or damaged ones.
A well-understood example is the intestinal lining, which renews itself every few days. Wnt signaling is active in the intestinal crypts where stem cells reside, driving their proliferation to maintain this turnover. The cycling of hair follicles is also regulated by Wnt signals that influence follicle stem cells.
The pathway participates in bone remodeling, a process where old bone is removed and new bone is created. By influencing bone-forming and bone-resorbing cells, Wnt signaling helps maintain bone density and strength in tissues like the skin and bone marrow.
Connection to Disease
Because the Wnt pathway governs cell growth, errors in its regulation are linked to many human diseases. Improper activation can lead to the uncontrolled cell division characteristic of cancer. Many tumors have mutations that cause the Wnt pathway to be permanently “stuck-on,” providing a constant signal for cells to multiply.
Colorectal cancer is a clear example of a disease driven by Wnt pathway defects. Many of these tumors have mutations in the APC gene, a component of the complex that normally destroys β-catenin. When APC is mutated, β-catenin accumulates and continuously activates genes that drive cell growth and tumor formation.
Faulty Wnt signaling is also implicated in other conditions. Dysregulation can contribute to bone density diseases like osteoporosis or conditions of excessive bone growth. It is also linked to metabolic disorders, such as type 2 diabetes, and cardiovascular diseases.