20-P002 Pre-enteric migration of sacral neural crest cells is affected in Dominant megacolon embryos

MECHANISMS OF DEVELOPMENT

1 2 6 ( 2 0 0 9 ) S 3 0 5 –S 3 1 3

available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/modo

Cell migration 20-P001

and experimental techniques including cell labelling, whole

Modeling the dynamic interactions that lead to the self-organi-

embryo culture and multiple immunohistochemical staining were

zation of the lateral line system

used. We found that in wild type embryos, sacral NCCs caudal to

Miho Matsuda1, Damian Dalle Nogare1, David Heredia2,

somite 24 began their migration from the neural tube at E9.5,

Ajay Chitnis1

started to aggregate on two sides of the hindgut to form pelvic gan-

1

NICHD NIH, Bethesda, MD, United States

glia at E11.5 and by around E14.0 entered the hindgut at S2 and S3

2

University of Louisville, Louisville, KY, United States The posterior lateral line primordium (pLLp) migrates caudally

vertebral levels. In Sox10Dom heterozygous mutants, sacral NCCs migrated along the same spatio-temporal pathway, although the number of migrating sacral NCCs was significantly reduced. In

and periodically deposits neuromasts under the skin in the zebra-

Sox10Dom homozygotes, the number of migrating sacral NCCs was

fish trunk and tail. Each neuromast, formed within the migrating

further reduced and no NCCs reached the pelvic ganglia region.

pLLp, has a central atoh1-positive hair cell determined by Notch

TUNEL assay did not reveal any significant increase in sacral NCC

mediated-lateral inhibition. The generation of new neuromasts

death in either Sox10Dom/+ or Sox10Dom/Dom mutants. Our observa-

and their deposition as the pLLp migrates caudally is coordinated

tions indicate that the Sox10 mutation in Dom embryos affects

by mutually antagonistic signaling centers; a Wnt signaling cen-

the migration of sacral NCC before they enter the hindgut by reduc-

ter at the leading edge and a FGF signaling center in the adjacent

ing the number of migrating sacral NCCs.

trailing domain, which determines both the morphogenesis of

Acknowledgements. The work was supported by General

epithelial rosettes and expression of atoh1 in the forming neuro-

Research Funds from the Research Grants Council of the Hong

masts. We have now shown that the central atoh1 expressing cell

Kong Special Administrative Region, China (Project No. 461808)

in the neuromast also plays a critical role in regulating FGF signal-

and a Direct Grant for Research 2008.1.009.

ing. When Notch signaling fails, too many cells express atoh1 and this eventually leads to failure of FGF signaling and unregulated

doi:10.1016/j.mod.2009.06.835

Wnt signaling. This eventually leads to collapse and disorganization of the migrating pLLp. Computational modeling reveals how interaction between these three signaling systems and differen-

20-P003

tial regulation of chemokine receptors regulates morphogenesis

Cell volume and tissue shape direct cell migration in a skin

and migration of the pLLp. The modeling also predicts a key role

explant model

played by negative feedback in the self-organization of this

Donald Ferris, Elizabeth Rugg

remarkable system. doi:10.1016/j.mod.2009.06.834

University of California Irvine, Irvine, CA, United States Coordinated cell movement is a widespread phenomenon in biology. During embryogenesis cell migration is essential for normal development. Although much is known about the mecha-

20-P002

nisms underlying individual cell migration, the factors driving

Pre-enteric migration of sacral neural crest cells is affected in

coordinated cell movement are still the subject of debate. Orien-

Dominant megacolon embryos

tated cell division, cell–cell intercalation and chemotaxis have

Xia Wang1, Alan J Burns2, Wood Yee Chan1 1

Department of Anatomy, Faculty of Medicine, The Chinese University of

Hong Kong, Hong Kong, China 2

Neural Development Unit, UCL Institute of Child Health, London,

United Kingdom

been proposed as mediators but none can fully account for the initiation of the vortex motion observed during processes such as primitive streak formation. We have observed a similar vortex motion during wound healing in a skin explant model and have used this model to investigate the mechanisms underlying the initiation of mass cell movement. The model comprised the cul-

Our previous study showed that mouse neural crest cells (NCCs)

ture of full thickness axolotl (Ambystoma mexicanum) limb skin

from the sacral level were able to migrate from the dorsal neural

into which central wounds were introduced. Cell movement and

tube over long distances to enter the hindgut. In the present study,

changes in morphology during wound healing were followed by

we sought to determine whether Sox10 mutation affected the

time-lapse microscopy and analyzed by image correlation spec-

migration of sacral NCCs prior to their entry to the hindgut. Domi-

troscopy. We identified a marked increase in cell volume (>30%)

nant megacolon (Dom) mice with a spontaneous mutation of Sox10,

preceding cell migration. Exposure of explants to hyperosmotic