The mouse is a traditional model organism for understanding physiological processes in humans. Chen-Ming Fan uses the mouse to study the underlying mechanisms involved in human development and genetic diseases. He concentrates on identifying and understanding the signals that direct the musculoskeletal system to develop in the mammalian embryo. Skin, muscle, cartilage, and bone are all derived from a group of progenitor structures called somites. Various growth factors—molecules that stimulate the growth of cells—in the surrounding tissues work in concert to signal each somitic cell to differentiate into a specific tissue type.

The lab has identified various growth factors that have profound effects on somite development. The goal of the lab is to identify more factors, the pathways in which they operate, and the genes that control the processes.

They identified that the Hedgehog (Hh) proteins are responsible for inducing the early skeletal fate and an unexpected mechanism that provides a new vision of the signaling pathway of Hh. They also found that  the Wnt family of proteins plays a key role in inducing the skin/muscle dual potential progenitors and they  have uncovered previously unknown effectors and target genes of Wnt.

Somites not only supply cells for embryonic muscles, they also contain muscle progenitors.  It turns out that the genes that make muscle stem cells in the embryo are surprisingly not needed in adult muscle stem cells to regenerate muscles after injury. The finding challenges the current course of research into muscular dystrophy, muscle injury, and regenerative medicine, which uses stem cells for healing tissues, and it favors using age-matched stem cells for therapy.

Researchers in the lab also study hormones involved with the hypothalamus, the essential brain center that maintains a balance of metabolic processes by modulating pituitary hormone secretions.  Studies of these hormones have been instrumental to our understanding of endocrine homeostasis, including the maintenance of proper concentrations of bodily fluid and the balance of energy metabolism.

Several genes, called Sim1, Sim2, and Gas1 are involved in musculoskeletal development. Sim1 also controls the developing hypothalamus.  The researchers found to their surprise that Sim1-heterozygous mice—having a pair of genes that are dissimilar for a hereditary characteristic—become obese from an uncontrollable appetite.  Human patients that are heterozygous for the Sim1 gene also display very early onset obesity. Since the hypothalamus has been implicated in the control of satiety, the researchers probe how Sim1 fits into the known genetic pathway involved in the obese condition.

Fan received his Ph. D. from Harvard University. He was a postdoctoral fellow at UC-San Francisco before coming to Carnegie as a staff researcher in 1995. For more see the Fan lab

 

Scientific Area: 
Genetics & Developmental Biology
Project(s): 
Understanding the musculoskeletal and hypothalamic systems

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Heart Reef in Australia's Great Barrier Reef, public domain.
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