Childs
lab, University of Calgary
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Elucidating
zebrafish angiogenesis:
We are taking a genetic
approach to identify new genes involved in angiogenesis, the process by which
new blood vessels develop. The cardiovascular system is critical for the
survival of vertebrates, and is one of the earliest organ systems to develop
in an embryo. Our experimental approach is to identify mutant animals with
defects in cardiovascular development during embryogenesis, and then to clone
the gene underlying each defect. We then examine the role of these genes in
embryonic development and disease. Angiogenesis is altered in many
diseases; for instance, it is increased during tumor growth and in diabetic
retinopathy. In other cases, impaired angiogenesis can also lead to disease,
for instance, in ischemia. The understanding of genes controlling blood
vessel growth may therefore lead to new treatments for disease. Zebrafish are a
common tropical fish that develop as transparent, externally fertilized
embryos. We can observe their development during all stages of
embryogenesis under a microscope, in contrast to mammals which develop in utero and are inaccessible. We use zebrafish as a model system because
they are small, transparent, and their cardiovascular system develops very
similarly to that of mammals. This allows us to do very detailed screens for
subtle genetic defects. Each pair of zebrafish lays a large number of eggs
each week. This greatly facilitates genetic analysis. Furthermore, as the
zebrafish genome is sequenced, it is clear that essentially all of the known
genes involved in the establishment of the early vascular system are
conserved between fish and mammals. Lab projects: • Vascular patterning • Vascular
specification • Origins of vascular
and visceral smooth muscle in zebrafish • Genetic pathways
leading to vascular stabilization |
Recent Publications: 1. Whitesell,
T.R., Kennedy, R.M., Carter, A.D., Rollins, E.L., Georgijevic,
S., Santoro, M.M. & Childs, S.J. An alpha-Smooth Muscle Actin (acta2/alphasma) Zebrafish Transgenic Line Marking Vascular
Mural Cells and Visceral Smooth Muscle Cells. PLoS One 9, e90590 (2014). 2. Tamplin, O.J., Durand, E.M., Carr, L.A., Childs, S.J.,
Li, P., Yzaguirre, A.D., Speck, N.A. & Zon, L.I. Live imaging of hematopoietic stem cell
lodgement reveals dynamic endothelial niche remodeling. Cell Accepted, In Press (2014). 3. Sarsons, C.D., Yaehne, K., Tekrony, A., Childs, S.J., Rinker, K.D. & Cramb, D.
Testing nanoparticles for angiogenesis-related disease: Charting the fastest
route to the clinic. Journal of
Biomedical Nanotechnology 10, 1641-1676 (2014). 4. French,
C.R., Seshadri, S., Destefano,
A.L., Fornage, M., Arnold, C.R., Gage, P.J., Skarie, J.M., Dobyns, W.B.,
Millen, K.J., Liu, T., Dietz, W., Kume, T., Hofker, M., Emery, D.J., Childs, S.J., Waskiewicz, A.J. & Lehmann, O.J. Mutation of FOXC1
and PITX2 induces cerebral small-vessel disease. J Clin Investigation 124,
4877-4881 (2014). 5. Ebert,
A.M., Childs, S.J., Hehr, C.L., Cechmanek,
P.B. & McFarlane, S. Sema6a and Plxna2 mediate spatially regulated
repulsion within the developing eye to promote eye vesicle cohesion. Development 141, 2473-2482
(2014). 6. Yaehne, K., Tekrony, A.,
Clancy, A., Gregoriou, Y., Walker, J., Dean, K.,
Nguyen, T., Doiron, A., Rinker, K., Jiang, X.Y.,
Childs, S. & Cramb, D. Nanoparticle accumulation in angiogenic tissues:
towards predictable pharmacokinetics. Small
9, 3118-3127 (2013). 7. Zeng,
L. & Childs, S.J. The smooth muscle microRNA miR-145 regulates gut
epithelial development via a paracrine mechanism. Developmental Biology 367, 178-186 (2012). 8. Liu,
J., Zeng, L., Kennedy, R.M., Gruenig, N.M. &
Childs, S.J. betaPix plays a dual role in cerebral
vascular stability and angiogenesis, and interacts with integrin
alpha(v)beta(8). Developmental Biology
363, 95-105 (2012). 9. Ebert,
A.M., Lamont, R.E., Childs, S.J. & McFarlane, S. Neuronal expression of
class 6 semaphorins in zebrafish. Gene
Expr Patterns 12, 6 (2012). 10. Chik, J.K., Schriemer,
D.C., Childs, S.J. & McGhee,
J.D. Proteome of the Caenorhabditis elegans oocyte. J Proteome Res 10, 2300-2305
(2011). 11. Zuccolo, J., Bau, J.,
Childs, S.J., Goss, G.G., Sensen, C.W. & Deans, J.P. Phylogenetic
analysis of the MS4A and TMEM176 gene families. PLoS One 5, e9369 (2010). 12. Mably, J.D. & Childs, S.J. Developmental Physiology
of the Zebrafish Cardiovascular System, in Fish Physiology:Zebrafish,
Vol. 29. (eds. S.F. Perry, M. Ekker, A.P. Farrell
& C.J. Brauner) 249-287 (Academic Press, 2010). 13. Lamont,
R.E., Vu, W., Carter, A.D., Serluca,
F.C., MacRae, C.A. & Childs, S.J. Hedgehog signaling via angiopoietin1 is required for
developmental vascular stability. Mech Dev 127,
159-168 (2010). 14. Christie,
T.L., Carter, A., Rollins, E.L. & Childs, S.J. Syk and Zap-70 function
redundantly to promote angioblast migration. Dev Biol 340, 22-29 (2010). 15. Zeng,
L., Carter, A.D. & Childs,
S.J. miR-145 directs intestinal maturation in zebrafish. Proc Natl Acad Sci U S A 106,
17793-17798 (2009). 16. Lamont,
R.E., Lamont, E.J. & Childs,
S.J. Antagonistic interactions among Plexins regulate the timing of
intersegmental vessel formation. Dev Biol 331, 199-209 (2009). |
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