"It seems probable that they are merely
anomalous, rudimentary structures with no function."
- Fawcett on Aberrant
Solitary Cilia, The Cell, 2nd Edition, 1981
The development of a complex organism from a fertilized
egg, one of biology's most astonishing transformations,
relies on intercellular communication. Developmental
genetics has successfully identified many of the signals
that nature deploys to coordinate this development, and
abnormalities in these signaling pathways underlie many
diseases. Our lab uses the fruits of a large-scale mouse
gene trap screen, as well as more classical mouse and
zebrafish genetic tools, to identify novel intercellular
Our genetic studies have led us to a specific interest
in the primary cilium, a somewhat mysterious organelle.
Most famously, primary cilia create the flow in the
mouse node important for left-right axis formation.
However, primary cilia exist on many other cells where
their functions are unknown. We have uncovered a novel
class of secreted factors conserved throughout metazoan
evolution that are important regulators of ciliogenesis.
Mutation of the founding member of this family results
in a wide variety of developmental defects. Currently,
we are using this mutant to elucidate the developmental
functions of cilia.
Recently, others have shown that ciliary defects
abrogate signaling by Hedgehog proteins. Defects in
Hedgehog signaling are important causes of congenital
birth defects and cancers. We have discovered that
Smoothened, an essential component of the Hedgehog
signaling pathway, moves to the primary cilium in
response to Hedgehog stimulation. As disrupting this
translocation prevents Hh signal transduction, we
believe that the primary cilium is the site at which
vertebrate Smoothened functions. We hypothesize that the
cell's primary cilium acts as an antenna through which a
variety of signals are sensed and transduced. Presently,
we are investigating how those signals participate in
development and disease.
Our last aim is to use our knowledge of these signals
to direct the differentiation of embryonic stem cells
along defined lineages. Of particular interest is
directing stem cells to become endodermal cells such as
pancreatic cell types. The ultimate goal of the Reiter
lab is to illuminate the function of novel signals in
vertebrate development and to use our understanding of
these signals to direct stem cells to become
therapeutically useful cell types.