Human development begins with a single cell that multiply and transition into all the structures and organs in the human body. This process depends upon precise communication between dividing cells while they coordinate their activities and actions. This communication is known as cell signaling, which is crucial for proper development. One small change in the signaling pathways between cells during development can result in a host of different types of complications, ranging from birth defects and cancer. A study published online on April 30 in the journal Developmental Cell by researchers at the Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA significantly advances the understanding of two major signaling pathways linked to hundreds of diseases. The findings made lead to treatment or prevention for this wide range of disease processes.
The study authors note that approximately seven key cell signaling pathways are essential for fetal development. After birth, these pathways continue to be important for the maintenance of bodily systems throughout life. However, how different signaling pathways interconnect and influence cell development is currently unknown. The researchers used the developing spinal cord and neural stem cells as a model to clarify two of the most fundamental pathways in cell development, “Notch” and “Sonic Hedgehog”, with the goa; of determining how the two pathways interact with each other. The research shows a significant connection between these two pathways as they work together to influence fetal development.
Senior author Bennett Novitch, PhD, a UCLA associate professor of neurobiology, explained, “Our study is the first to suggest a mechanistic connection between Notch and Sonic Hedgehog signaling pathways; we found that the activity of the Notch pathway alters the activity of the Sonic Hedgehog pathway. It’s an unexpected convergence of two of the most important developmental signaling pathways.”
Several mechanisms are involved in the process of cell signaling, including the type of signal, the amount of the signal the cell receives, the time cells are exposed to the signal, the state of the cells during signaling, and how the signal is processed by the cell. The researchers attempted to understand how all of these factors influence neural stem cells exposed to Notch and Sonic Hedgehog signaling.
The authors explain that Notch signaling is essential because it has the ability to expand progenitor (cells that develop into different types of mature cells) cells when stimulated and reduce progenitor cells when inactivated. All embryonic stem cells start in a pluripotent state, meaning they can develop into any cell in the body, as development progresses, the cells are dispatched to different parts of the body. Progenitor cells can divide a limited number of times to produce cells within their designated tissue type. For example, a pluripotent stem cell can become a neural cell or a blood cell; however, a neural progenitor cell can only develop into different cells within the nervous system and cannot become a blood cell. Where progenitor cells are present in the body, Notch signaling also exists, which is needed to maintain the progenitor state. If Notch signaling does not occur, cells cease to maintain a progenitor state and are no longer capable of replicating.