Snail is a transcription factor, a protein that binds to specific DNA sequences to control the flow of genetic information from DNA to messenger RNA. Part of the “Snail family” of zinc-finger proteins, Snail and related proteins Slug and Smuc play a role in cellular instruction. These proteins act as master switches, turning specific genes “on” or “off” to direct a cell’s identity and behavior.
The structure of Snail proteins includes a highly conserved region with C2H2-type zinc fingers, which allows them to bind to a specific DNA sequence known as an E-box. At the other end, vertebrate Snail proteins possess a SNAG domain, which is instrumental for their function as transcriptional repressors. This ability to repress gene expression is central to how Snail directs cellular processes.
Snail’s Role in Embryonic Development
The Snail transcription factor is a necessary component of embryonic development, orchestrating complex cellular movements. One of its primary functions occurs during gastrulation, an early embryonic stage where a simple structure of cells reorganizes into three distinct germ layers. These layers—the ectoderm, mesoderm, and endoderm—are the foundational tissues for all organs and bodily structures. Snail is active in the formation of the mesoderm.
Snail also provides “cellular travel instructions” for specialized embryonic cells known as neural crest cells. During development, these cells must detach from their initial location along the neural tube and migrate throughout the embryo. This migration is necessary for the formation of a wide array of tissues.
The journey of neural crest cells gives rise to diverse components of the body. These include the peripheral nervous system, pigment-producing melanocytes in the skin, and cartilage and bone in the skull and face. Without the instructions provided by Snail, this cellular dispersion would not occur correctly, leading to significant developmental abnormalities.
How Snail Changes Cell Behavior
Snail alters cell behavior by initiating a process known as the Epithelial-Mesenchymal Transition (EMT). EMT is a biological program where epithelial cells, which are stationary and tightly bound in sheets, transform into mesenchymal cells. Mesenchymal cells are characterized by their loose organization and capacity for movement, allowing them to migrate and invade surrounding tissues.
The core of Snail’s mechanism is its ability to act as a transcriptional repressor, targeting the gene that produces E-cadherin. E-cadherin functions as a molecular glue, a protein that holds epithelial cells together, maintaining the structural integrity of the tissue. By binding to the E-cadherin gene’s promoter region, Snail shuts down its production.
When the “molecular glue” is no longer synthesized, the tight connections between epithelial cells dissolve. This loss of adhesion allows individual cells to break free from the formerly cohesive sheet. Freed from their stationary positions, the cells change shape and internal structure, adopting the migratory characteristics of mesenchymal cells.
Snail’s Involvement in Disease Progression
While the Epithelial-Mesenchymal Transition is a normal process during embryonic development, its re-activation in adult tissues can have pathological consequences. The same Snail-driven mechanism can be hijacked by cancer cells to facilitate metastasis. Cancer cells within a primary tumor can then utilize Snail to undergo EMT, breaking away from the original tumor mass.
Once cancer cells have transitioned into a mesenchymal state, they can invade nearby tissues and enter the bloodstream or lymphatic system. This mobility allows them to travel to distant sites in the body and establish secondary tumors, the primary cause of mortality in many cancer patients. The expression of Snail in tumors is correlated with increased invasion and a poorer prognosis.
Beyond cancer, Snail is also implicated in fibrosis, a condition of excessive scar tissue formation in organs like the lungs, liver, and kidneys. In fibrotic diseases, Snail can promote the transition of epithelial cells into matrix-producing fibroblasts. These activated fibroblasts deposit large amounts of extracellular matrix proteins, leading to tissue hardening, organ dysfunction, and eventual failure.