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Newswise TEMPE, Ariz. By understanding the secret of how lizards regenerate their tails, researchers may be able to develop ways to stimulate the regeneration of limbs in humans. Now, a team of researchers from Arizona State University is one step closer to solving that mystery. The scientists have discovered the genetic recipe for lizard tail regeneration, which may come down to using genetic ingredients in just the right mixture and amounts.

An interdisciplinary team of scientists used next-generation molecular and computer analysis tools to examine the genes turned on in tail regeneration. The team studied the regenerating tail of the green anole lizard (Anolis carolinensis), which when caught by a predator, can lose its tail and then grow it back.

The findings are published today in the journal PLOS ONE.

"Lizards basically share the same toolbox of genes as humans," said lead author Kenro Kusumi, professor in ASU's School of Life Sciences and associate dean in the College of Liberal Arts and Sciences. "Lizards are the most closely-related animals to humans that can regenerate entire appendages. We discovered that they turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals and wound healing.

Other animals, such as salamanders, frog tadpoles and fish, can also regenerate their tails, with growth mostly at the tip. During tail regeneration, they all turn on genes in what is called the Wnt pathway a process that is required to control stem cells in many organs such as the brain, hair follicles and blood vessels. However, lizards have a unique pattern of tissue growth that is distributed throughout the tail.

"Regeneration is not an instant process," said Elizabeth Hutchins, a graduate student in ASU's molecular and cellular biology program and co-author of the paper. "In fact, it takes lizards more than 60 days to regenerate a functional tail. Lizards form a complex regenerating structure with cells growing into tissues at a number of sites along the tail.

"We have identified one type of cell that is important for tissue regeneration," said Jeanne Wilson-Rawls, co-author and associate professor with ASUs School of Life Sciences. "Just like in mice and humans, lizards have satellite cells that can grow and develop into skeletal muscle and other tissues."

"Using next-generation technologies to sequence all the genes expressed during regeneration, we have unlocked the mystery of what genes are needed to regrow the lizard tail," said Kusumi. "By following the genetic recipe for regeneration that is found in lizards, and then harnessing those same genes in human cells, it may be possible to regrow new cartilage, muscle or even spinal cord in the future."

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How Lizards Regenerate Their Tails: Researchers Discover Genetic 'Recipe'

NIH-supported study suggests that early diagnosis of severe combined immunodeficiency leads to high survival rates

A newborn screening test for severe combined immunodeficiency (SCID) reliably identifies infants with this life-threatening inherited condition, leading to prompt treatment and high survival rates, according to a study supported by the National Institutes of Health. Researchers led by Jennifer Puck, M.D., of the University of California, San Francisco, also found that SCID affects approximately 1 in 58,000 newborns, indicating that the disorder is less rare than previously thought. The study was funded in part by NIHs National Institute of Allergy and Infectious Diseases (NIAID) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in the Aug. 20 issue of the Journal of the American Medical Association.

Blood is collected from a newborn for screening. Credit: U.S. Air Force photo/Staff Sgt Eric T. Sheler

SCID is a group of disorders caused by defects in genes involved in the development and function of T cells and other infection-fighting immune cells. Infants with SCID are highly susceptible to life-threatening infections. SCID is fatal, usually within the first year or two of life, unless affected infants are given immune-restoring treatments such as transplants of blood-forming stem cells or gene therapy. More than 80 percent of affected infants do not have a family history of the condition.

The results of this study highlight the important role of newborn screening for SCID, said NIAID Director Anthony S. Fauci, M.D.The findings demonstrate that detecting SCID before symptoms such as severe infections appear helps ensure that infants with this serious condition receive lifesaving treatments.

The SCID newborn screening test, originally developed at NIH, measures T cell receptor excision circles (TRECs), a byproduct of T-cell development. Infants with SCID have few or no T cells, regardless of the underlying genetic defect, and the absence of TRECs may indicate SCID.The TREC test also may help doctors identify infants with non-SCID T-cell deficiencies. SCID was added in 2010 to the U.S. Department of Health and Human Services Recommended Uniform Screening Panel for newborns in the United States. However, the TREC test has not yet been adopted universally. Nearly half of states conduct newborn screening for SCID, and the test is performed for almost two thirds of infants born across the country.

We have made great strides in our knowledge of SCID and other related immunodeficiencies in a relatively short period of time, thanks to newborn screening, said Tiina Urv, Ph.D., a program director in the Intellectual and Developmental Disabilities Branch at NICHD. Such collaborative research efforts could serve as a model for other disorders.

The current study evaluated data from more than 3 million newborns gathered by screening programs in 10 states and the Navajo Nation, which spans parts of Arizona, New Mexico and Utah. Navajo have a higher than average risk of SCID, due to certain genetic mutations. Overall, screening detected 52 newborns with SCID, equivalent to 1 in 58,000 infants. All infants with abnormal TREC results underwent further diagnostic testing to confirm SCID. The researchers did not identify any cases of SCID that were missed by TREC screening. Previous estimates, based on limited data, suggested that SCID was less prevalent, affecting only 1 in 100,000 babies.

Early diagnosis allows physicians to treat SCID infants promptly, before infections become overwhelming. Of the 52 SCID infants in the current study, 49 received immune-restoring therapies such as stem cell transplants, enzyme replacement therapy or gene therapy. Three infants died before treatment was given. Four died after receiving transplants, while the other 45 treated infants (92 percent) survived. A recent NIH-funded study showed that SCID infants who received stem cell transplants early in life (less than 3.5 months old) and before the onset of infections had the best outcomes.

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