Childs lab,
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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: Christie TL, Carter
A, Rollins EL, Childs SJ. Syk and Zap-70 function redundantly to
promote angioblast migration. Developmental Biology. 2010 Apr 1;340(1):22-9. Lamont RE, Vu W,
Carter AD, Serluca FC, Zuccolo J, Bau
J, Childs SJ, Goss GG, Sensen CW, Deans JP. Phylogenetic analysis of
the MS4A and TMEM176 gene families. PLoS One. 2010 Feb 23;5(2):e9369. Zeng L, Carter
AD, Childs SJ. miR-145 directs intestinal
maturation in zebrafish. Proc Natl Acad Sci Lamont RE, Lamont
EJ, Childs SJ. Antagonistic interactions among Plexins regulate
the timing of intersegmental vessel formation. Developmental Biology.
2009 Jul 15;331(2):199-209. J. Liu, S. D. Fraser, P. W. Faloon,
E. L. Rollins, J. Vom Berg, O. Starovic-Subota, A. L. Laliberte,
J. N. Chen, F. C. Serluca and S. J.
Childs. (2007). A bPix-Pak2a signaling pathway regulates cerebral
vascular stability in zebrafish. Proc
Natl Acad Sci U S A 104, 13990-13995. S. Georgijevic, Y.
Subramanian, E. L. Rollins, O. Starovic-Subota, A. C. Tang and S. J. Childs. (2007). Spatiotemporal
expression of smooth muscle markers in developing zebrafish gut. Dev Dyn 236, 1623-32. D. C. Callander, R. E. Lamont, S. J. Childs and S. McFarlane.
(2007). Expression of multiple class three semaphorins in the retina and
along the path of zebrafish retinal axons. Dev Dyn 236, 2918-2924. R. E. Lamont
and S. Childs. (2006). MAPping out
arteries and veins. Sci STKE 2006,
pe39. T. L. Christie, O.
Starovic-Subota and S. Childs.
(2006). Zebrafish collapsin response mediator protein (CRMP)-2 is expressed
in developing neurons. Gene Expr
Patterns 6, 193-200. J. Torres-Vazquez, A. D. Gitler, S. D. Fraser, J. D. Berk, N.
P. Van, M. C. Fishman, S. Childs,
J. A. Epstein and B. M. Weinstein.
(2004). Semaphorin-plexin signaling guides patterning of the developing
vasculature. Dev Cell 7,
117-23. *
Note the first three authors and senior three authors made an equal
contribution to this publication. B. L. Roman, V. N. Pham, N. D. Lawson, M. Kulik, S. Childs, A. C. Lekven, D. M. Garrity, R. T. Moon, M. C.
Fishman, R. J. Lechleider and B. M. Weinstein. (2002). Disruption of acvrl1 increases endothelial cell number
in zebrafish cranial vessels. Development
129, 3009-3019. D. M. Garrity, S. Childs
and M. C. Fishman. (2002). The
heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome.
Development 129, 4635-45. S. Childs, J.-N. Chen, D. Garrity and M.
Fishman. (2002). Patterning of
angiogenesis in the zebrafish embryo. Development
129, 973-982. T. Zhong, Childs, S, Liu,
JP, Fishman, MC. (2001). Gridlock
signaling pathway fashions the first embryonic artery. Nature 414, 216-220. R. Wang, M. Salem, I. M. Yousef, B. Tuchweber, P. Lam, S. J. Childs, C. D. Helgason, C.
Ackerley, M. J. Phillips and V. Ling.
(2001). Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice
results in nonprogressive but persistent intrahepatic cholestasis. Proc Natl Acad Sci U S A 98,
2011-6. S.
Childs, B. M.
Weinstein, M. A. Mohideen, S. Donohue, H. Bonkovsky and M. C. Fishman. (2000). Zebrafish dracula encodes
ferrochelatase and its mutation provides a model for erythropoietic
protoporphyria. Curr Biol 10,
1001-4. * Note the first two authors made an equal
contribution to this publication. |
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Heart and Stroke Foundation of Natural Science and Engineering Research
Council |
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