NICHD research on normal and atypical developmental processes at the molecular and cellular levels continues to move biomedical science toward possible diagnostic and therapeutic breakthroughs for some of the most devastating disorders of children and adults. New findings on adult stem cells, molecular mechanisms of birth defects, and genes associated with type 1 diabetes and with two rare genetic disorders that cause severe disabilities raise the possibility of, ultimately, being able to ameliorate or prevent these conditions.

Adult stem cells that started down a path of becoming a specific cell can be experimentally manipulated to change their mind and return to their original status as a stem cell. Stem cells are unspecialized cells, found in animals and humans. Stem cells have unique capacities to renew themselves and to give rise to specialized cells with specific shapes and functions such as muscle cell contraction or nerve cell signaling. Adult stem cells are found in specialized tissues of adults and yield cell types of the tissue from which they originate. Scientists have long assumed that once a stem cell begins to "differentiate" - that is, to become a tissue-specific cell - it loses its capacity to self-renew. This assumption was turned on its head when scientists used sophisticated genetic techniques to cause germ line stem cells of adult fruit flies to revert back to their original status, capable of self-renewal, after the cells had initiated the process of differentiating into sperm cells.[1] Although fruit flies differ in many ways from higher organisms such as humans, the signaling pathways that cells use to carry out their functions are remarkably similar in all organisms. Understanding the differentiation process of cells in fruit flies could solve a major puzzle for developmental biologists. It also means that stem cells in humans could have the same ability to revert back to their original status after starting to differentiate. This unique ability could one day lead to new therapeutic approaches for multiple disorders.

Different birth defects result from two signaling pathways on a molecule. Cells need to continuously monitor and integrate environmental cues to ensure proper development of the embryo and to maintain homeostasis or stability of tissues in adults. To understand how these monitoring and integrating processes are regulated, scientists need to understand how different cues or signals interact at the molecular level to regulate cell activity. Researchers recently discovered two different signaling pathways on the same molecule, each of which resulted in a different birth defect in an experimental mouse model.[2] This research was the first to show that mutations in different parts of one protein, which plays a critical role in two different signaling pathways, can cause different developmental defects. In addition, new understanding of how a cell can interpret different signals in its environment can assist scientists in directing naïve cells, such as adult stem cells, to develop into a specific type of cell that can repair tissue.

New gene identified in type 1 diabetes. Researchers have identified more than twenty chromosomal regions that are linked to type 1 diabetes, a type of disease in which the body's immune system attacks the body's tissues. Until now, however, researchers had not found an individual gene associated with the disease. NICHD-supported scientists recently discovered a mutated gene in one of the previously-identified chromosomal regions and showed how the gene is causally linked to type 1 diabetes.[3] The gene makes a type of protein that has a critical, indirect role in regulating the immune system. The mutation in the gene interferes with the action of the protein. The scientists found that patients with type 1 diabetes were more likely to have the mutated gene. Moreover, they learned that the gene was expressed at varying levels in the patients' immune tissues, with the highest levels in the lymph nodes and the spleen. The discovery of the previously unknown regulatory pathway in origin and development of type 1 diabetes gives scientists new targets for future genetic and immunological treatments of the disease.

Rett syndrome protein involved in early development. Rett syndrome (RTT) is a genetic disorder that gradually halts the healthy development of infant and toddler girls. Among other problems, girls with RTT lose their ability to talk, to interact with other people and to move independently. Currently, no treatment exists to halt its progression. Researchers have determined that the disorder results from a defect in a particular gene, known as MeCP2, but were unsure of the gene's function. Recently, scientists gained an understanding of the gene's function by studying the underwater frog, Xenopus. The researchers determined that a mutant form of the gene affects early embryonic development, resulting in an excess number of the precursor cells that give rise to the brain. Xenopus tadpoles with the mutant gene developed neurological anomalies similar to those seen in RTT.[4] The researcher's findings contribute to an improved understanding of RTT, which may eventually lead to new treatments for the disorder.

Gene discovered for Cornelia de Lange Syndrome. For the first time, scientists have found a mutated gene that is associated with Cornelia de Lange Syndrome, a rare, multi-system disorder characterized by mental retardation, heart defects, and multiple other physical and behavioral anomalies.[5] Researchers studied 12 families in which one or more members have the disorder and identified a gene that had multiple mutations and that was widely expressed in fetal and adult tissues. The gene appears to be involved in the very early stages of embryonic development, and contains information needed to switch on a number of other genes during that period. The gene's discovery is expected to speed development of a prenatal test for the syndrome. A similar test will also be developed to diagnose Cornelia de Lange Syndrome in young children who may have the condition. Discovery of the gene is an important step not only toward understanding and helping to diagnose the disorder, but for possibly developing future interventions to prevent it.