They are hugely important little dudes, those genes called Wnts.
An amalgam of "wingless" and "int," the term Wnt derives from the
first two members of the gene family to be discovered: wingless
(Drosophila, or fruit fly) and int-1 (mouse). Wnts are
signaling proteins that control many cell processes in a variety
of different organisms, including mammals. They play crucial roles
in early development, regulating cell proliferation, polarity,
differentiation, migration and fate.
They are also implicated in disease. The most famous example is
breast cancer, when Wnt genes, normally silent, are activated by
Summer students participating in the 2006 Summer Residency Program
got a full-court introduction to Wnts in Dr. Yingzi Yang's recent
lecture, "The Making of Skeletons."
Yang studies cell-to-cell signaling in vertebrate limb development
and skeletal morphogenesis. A fundamental aspect of developmental
biology, morphogenesis concerns how the body's structures are generated,
positioned, shaped and specialized.
|Dr. Yingzi Yang
As NHGRI's section head of developmental genetics, Yang concentrates
on the Wnt and Hedgehog groups of signaling molecules. Her goal
is to understand precisely how these signaling pathways act and
interact with each other and with other signaling molecules in
regulating vertebrate embryonic development. She spoke to her audience
in Lipsett Amphitheater, where she offered a comprehensive overview
of her work.
To understand pathological mechanisms, she told them, we must
first understand normal biological processes. "However," she observed, "we
cannot do experiments on human beings, so to gain insight into
molecular pathways that govern embryological development we can
study other vertebrate species and see results applied directly."
The mouse, Yang explained, is the only available mammalian model
in which to do sophisticated genetic manipulation. She explained
reverse genetics, covering the creation of knockout, knock-in and
transgenic mice; and forward genetics, covering mutagenized mice
treated with chemicals or DNA insertions.
She then laid out results of several experiments that showed how
key aspects of skeletal development are controlled by Wnt signaling.
She focused on Wnt action upon chondrocytes — cells that
are cartilage-forming — and osteoblasts, the bone-forming
cells. Both are manipulated by blocking or enhancing Wnt signaling.
Yang showed how, in skeletal morphogenesis, Wnt signaling is critical
for later development. Receptors that are too active or inactive
affect bone density. Too much can lead to osteoarthritis; too little,
In conclusion, she showed how Wnt signaling helps us understand
the formation of healthy bone, cartilage and joint, with important
implications for treatment.