Protein maintains cross talk between cells that control hair growth
Exchange of signals between 2 types of skin cells may provide a new
understanding of how stem cells differentiate
Genes, it turns out, are only as active as the signals that turn them
on and off. Now scientists from Rockefeller University and the Howard
Hughes Institute have identified the signaling molecule that ratchets
up and clamps down the activity of key genes in dermal papilla, a
type of skin cell whose unique collection of proteins ultimately
instruct epithelial stem cells to make hair.
The research, which will be published in the February 15 issue of
Genes & Development, highlights the cross talk between these two cell
types and how this signaling molecule, a protein called BMP, is
crucial for this exchange.
Epithelial stem cells nest in the upper portion of the adult hair
follicle, and dermal papilla reside nearby in the mesenchymal layer
below them. It is thought that the communication signals between the
two cell types instruct the stem cells to form hair follicles during
embryogenesis, and then, when these follicles have matured, regulate
their cycles of hair growth and regeneration. "Scientists don't know
how dermal papilla cells are programmed to provide the instructive
signals to stem cells, but now we know that BMP signals play a
crucial role," says Michael Rendl, who conducted this work while he
was a postdoc in Elaine Fuchs's Laboratory of Mammalian Cell Biology
and Development.
For several years, it has been known that BMP signaling must be
reduced in order to activate follicle stem cells. "Michael has now
uncovered a new twist to the story," says Fuchs, who is Rebecca C.
Lancefield Professor at Rockefeller and an investigator at the Howard
Hughes Medical Institute, "namely that dermal papilla cells appear to
receive BMP signals from their surrounding microenvironment and this
signaling is required for these two cell types to maintain cross
talk."
Fuchs conducted the study with Rendl, who found that BMP6, a member
of the BMP family of proteins, orchestrates dermal papilla's
signature genes to turn on and off, thereby giving these skin cells
their unique collection of proteins and features.
Fuchs's team developed a clever strategy to delete several genes in
vitro, ones that encode for the receptor onto which several BMPs
bind. They then grafted these genetically engineered dermal papilla
cells onto the backs of bald mice to see if these mice would grow
hair.
Well, the mice didn't. When dermal papilla cells lacked this
receptor, their signature proteins were not expressed and the key
signaling that occurs between epithelial stem cells and dermal
papilla was impaired. Without this exchange, the hair follicles did
not grow or make hair.
Nearly all of the signature proteins that Rendl and Fuchs tested in
dermal papilla cells decreased when they deleted the BMP receptor.
The exception: BMP6 itself. This increase in BMP6 expression levels
suggests that BMP6 is necessary for both locking in dermal papilla's
molecular identity as well as maintaining the crosstalk that allows
stem cells to receive hair-inducing signals, but it itself is not the
signal that stem cells await. This finding also provides clues to the
type of signals that follicle stem cells may send to dermal papilla.
What's more, BMP6 specifically maintains the molecular identity of
dermal papilla cells. When Rendl and Fuchs induced the BMP pathway in
other cell types that respond to BMP signaling, they found that these
cells continue to produce the normal amount of their signature
proteins. "This was really interesting,
the case that different signaling pathways, or a combination of them,
regulate different sets of genes to give each cell type in the hair
follicle its characteristic properties."
Fuchs speculates that "this complex circuitry in BMP signaling may
set the foundations for a BMP regulatory clock that drives the hair
cycle. If so, we may be one step closer to unlocking nature's secrets
to hair growth."
###
This research was supported in part by the Tri-Institutional Stem
Cell Initiative, a collaborative program of three New York City
biomedical research institutions -- Memorial Sloan-Kettering Cancer
Center, The Rockefeller University and Weill Cornell Medical College.
Public release date: 14-Feb-2008
Contact: Thania Benios
tbenios@rockefeller
212-327-7146
Rockefeller University
http://www.eurekale
------------
More:
Public release date: 14-Feb-2008
Contact: Heather Cosel
coselpie@cshl.
Cold Spring Harbor Laboratory
BMP signaling, skin stem cells and hair formation
The February 15th cover story of G&D reports on the recent discovery
by Dr. Elaine Fuchs and colleagues at the Rockefeller University that
BMP signaling in dermal papilla cells is important for hair follicle
formation.
The dermal papilla (DP) is a small cluster of mesenchymal cells that
exist at the base of the hair follicle, and instruct nearby
epithelial stem cells to induce hair follicle growth. But because DP
cells are so few in number, and loose their hair-inducing potential
in culture, the details of this molecular conversation have remained
elusive.
Dr. Fuchs' team developed a clever genetic strategy to delete
specific genes of interest in DP cells, and then graft these
genetically engineered cells onto the backs of immunocompromised (and
bald) mice, to study the effect of gene deficiency on hair growth.
The researchers found that deletion of the receptor for the bone
morphogenetic protein 1a (BMPR1a) in DP cells prevented the formation
of hair follicles in engrafted mice. However, if BMPR1a is intact in
DP cells, and a bit more BMP protein is added to the cells, then the
DP-stem cell cross-talk is prolonged, and recipient mice grow a tuft
of hair on their otherwise bald backs.
"Several years ago, we devised a method to purify the cells and
characterize the genes expressed by the DP and its neighboring cells
that make hair," says Fuchs. "This gave us clues that BMP signaling
might be important in specifying the unique hair-inducing properties
of DP cells. We've now succeeded in testing this possibility and our
findings are important not only for our understanding of the
mesenchymal-
production, but also for developing new and improved methods for
stimulating hair growth."
http://www.eurekale
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