Our hearts are made of strong muscle that has one task: to pump blood day and night. Our faces, on the other hand, use 60 different muscles to smile, frown, chew or talk. A team of Institute scientists has now shown that the development of the one is closely tied to the development of the other.
In a series of three articles that appeared in the scientific journal Development, Dr. Eldad Tzahor and research students Libbat Tirosh, Ariel Rinon and Elisha Nathan of the Biological Regulation Department reported surprising findings that have come out of their research into the development of facial muscles in the embryo. Heart and skeletal muscles both arise from the middle layer of embryonic cells – the mesoderm – although their developmental programs are distinctly separate. These mesoderm cells are no longer embryonic stem cells that can become any kind of organ or tissue. Rather, they are progenitor cells – cells that are just beginning to “commit” to becoming a particular type of tissue, such as kidney or muscle.
The scientists, therefore, were astonished when they removed facial muscle progenitor cells from their “natural setting” in the embryo and grew them in a cell culture in the lab. The cells that appeared to be destined to become facial muscle developed into heart muscle and even began beating. This finding provides strong evidence that these mesoderm cells are equipped with a “default plan.” Normal embryonic development involves “cross-talk” between the developing cells, and previous research in Tzahor’s lab had shown that this ongoing discussion helps direct the various cells down a particular developmental path. It seems that in the absence of signals from other sources, the cells switch to the default plan and become heart cells.
Another study in Tzahor’s lab revealed that some of the mesoderm progenitors that contribute to the facial muscles actually end up in the heart and become ensconced in the heart tissue near the exits of the two large blood vessels, the aorta and the pulmonary artery. As these areas are particularly prone to congenital birth defects (about one in 100 newborns is diagnosed with a heart defect), these findings take on special significance for medical research. In this study, the team also identified a specific protein that directs the differentiation of the muscle progenitor cells into one of these two cell fates, skeletal muscle or heart. When they added this protein to early chicken embryos, their facial muscle progenitor cells began to exhibit some characteristics of heart cells.
Further studies brought more revelations. Oneof the differences long believed to exist between heart and skeletal muscle is that skeletal muscles can regenerate when damaged, whereas the heart was thought to be a non-renewable organ. But recent studies have identified specific heart muscle progenitor cells in the mesoderm that produce a protein known as Islet-1. Islet-1 is tied to the ability to regenerate, and cells producing it have been shown to migrate to various parts of the heart, where they are thought to act as “reserves.” Tzahor and his team tagged heart progenitor cells that produce Islet-1 in mouse and chicken embryos, to follow their development. To their great surprise, while some of these cells did indeed end up in the heart, others migrated to certain facial muscles, especially those that open the lower jaw.
What is the developmental connection between facial muscles and the heart? The answer, says Tzahor, may be rooted in our evolutionary past: In worms – creatures with no heart – the head muscles used for swallowing also function to keep the circulatory system moving. So the ties between the two may be remnants from an earlier developmental plan.
“The developmental processes in the heart and face are intricately tied to each other,” says Tzahor. “The complex interactions they engage in are precisely orchestrated and are vital to the healthy functioning of both. Solving the molecular component of their developmental plans is the key to understanding the genetic and cellular basis of the many birth defects that affect both heart and face.” In the future, this understanding may lead, among other things, to the development of ways to treat degenerative diseases that affect heart and skeletal muscle.
Dr. Eldad Tzahor’s research is supported by the Kekst Family Center for Medical Genetics; the Willner Family Leadership Institute for the Weizmann Institute of Science; and the Estelle Funk Foundation. Dr. Tzahor is the incumbent of the Gertrude and Philip Nollman Career Development Chair.
Taking the Lead
Yet another study by Tzahor’s team demonstrates the importance of communication between cells for healthy tissue development. Neural crest cells originate in the ectoderm, the outer layer of embryonic tissue, and they have the ability to differentiate into a wide variety of cell types. In the face, these cells give rise to most of the bone, cartilage and connective tissue. But the researchers found that these cells perform yet another function: They oversee the developmental plan for the facial muscles. Neural crest cells take those mesoderm cells slated to become facial muscle, “lead” them to the correct place on the developing head and instruct them to begin the process of differentiating into muscle tissue.