Areas of Interest
A major area of interest in the Dealy lab is to investigate
the molecular regulation of limb development in the vertebrate
embryo, from early stages during which the limb bud is
patterned, to later stages when differentiation of the skeletal
elements into cartilage and bone occurs. We are particularly
interested in the role that certain growth factors play in these
processes. We are using tissue-specific targeted transgenesis,
Cre-mediated gene deletion, and retroviral gene delivery to test
the roles of various growth factors and their receptors in
developing limbs and skeletal elements in mouse (and chick)
embryos in vivo.
Another area of interest is to investigate the signals and
conditions that control differentiation of human embryonic stem
cells. We are interested in directing the differentiation of
human ES cells into chondrocytes, with the eventual goal of
testing the potential therapeutic value of hES cell-derived
chondrocytes for repair of damaged or osteoarthritic joints.
These studies are being carried out in the context of a State of
CT funded human ES cell initiative that utilizes existing as
well as new hES cell lines.
Understanding the molecular mechanisms that regulate
cartilage and bone development is significant for human health,
as the ultimate goal of this research is to identify new targets
for future medical intervention in the treatment or prevention
of human skeletal conditions such as limb birth defects,
cartilage or bone dystrophy, or degenerative joint disease.
Lab Rotation Projects
Students may participate in ongoing projects in the lab,
including but not limited to the following:
- Examining the effects of targeted misexpression or
genetic deletion of growth factor receptors in the skeletal
elements of transgenic mice.
- Examining the effects of modulation of growth factor
signaling during in vitro differentiation of mouse
chondrocytes.
- Defining the signals that direct totipotent human
embryonic stem cells into the chondrocyte lineage.
Selected Publications
Li, Y., Toole, B.P., Dealy, C.N., and Kosher R.A. 2007.
Hyaluronan in limb morphogenesis. Submitted.
Fisher, M.C., Li, Y., Seghatoleslami, M.R., Dealy, C.N. and
Kosher, R.A. 2006. Heparan sulfate proteoglycans including
syndecan-3 modulate BMP activity during limb cartilage
differentiation. Matrix Biology, 25: 27-39.
Omi, M. Fisher, M., Maihle, N.J., and Dealy, C.N. 2005.
Studies on EGF receptor signaling in vertebrate limb patterning.
Developmental Dynamics, 233: 288-300.
Fisher, M. Meyer, C., Garber, G., and Dealy, C.N. 2005. Role
of IGFBP2, IGF-I and IGF-II in regulating long
bone growth. Bone, 37: 741-750.
Wang, C-K L., Omi, M., Ferrari, D., Cheng, H-C., Lizarraga,
G., Chin, H-J., Upholt, W.B., Dealy, C.N., and Kosher, R.A.
2004. Function of apical ectodermal BMPs in developing mouse
limbs. Dev. Biol. 269, 109-122.
Soufer, R., McQueeney, K., and Dealy, C.N. 2002. β-catenin-dependent
Wnt signaling in apical ectodermal ridge induction and FGF8
expression in normal and limbless mutant chick limbs.
Development, Growth & Differentiation, 44: 315-325.
McQueeney, K., and Dealy, C.N. 2001. Roles of insulin-like
growth factor-I (IGF-I) and IGF-I binding protein-2 (IGFBP2) and
–5 (IGFBP5) in developing chick limbs. Growth Hormone & IGF
Research 11: 346-363. |