Cell Migration During Embryonic Development

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Cell Migration During Embryonic Development
Jason Jessen jason.r.jessen_at_vanderbilt.edu Departm
ent of Medicine/ Division of Genetic
Medicine Department of Cancer Biology
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Migrating cancer and embryonic cells share many
features, both at the cellular and molecular
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Caudal migration of hindbrain motor neurons
Bingham et al., 2002
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Trinh and Stainier, 2004
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SDF1 ligand
CXCR4 receptor
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Germ cells are attracted to ectopic sources of
SDF1 ligand
Doitsidou et al., 2002
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Early germ cells are non-motile for a short
period after being specified - The cells are
round and extend protrusions in random directions
By 4.7 hpf, germ cells become polarized and begin
migrating
12 hpf germ cells transplanted to a 3 hpf host
embryo
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Molecular pathway controlling germ cell migration
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Convergence Extension cell movements shape the
embryo body plan
head
tail
6-12 hours post- fertilization (hpf)
Karlstrom and Kane (1996)
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Each germ layer contributes to Convergence
Extension
Solnica-Krezel Cooper, 2002 Pattern Formation
in Zebrafish, Springer-Verlag
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Epiboly
Jessen and Solnica-Krezel, 205
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Convergence Extension cell movements
Jessen and Solnica-Krezel, 205
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Cell fate and tissue patterning occur in
conjunction with Convergence Extension
Ventralized mutant
Dorsalized mutant
CE mutant
CE mutant
Myers et al., 2002
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Stat3 depleted embryos exhibit classical
Convergence Extension phenotypes
Yamashita et al., 2002
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Tools for quantifying gastrulation cell
movements Caged fluorescein DIC time-lapse
microscopy Confocal imaging
Yamashita et al., 2002
Myers et al., 2002
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Directed migration of lateral mesodermal cells
towards the dorsal embryonic axis
50-62 Epiboly Animalward Migration Epiboly
Extension
Sepich et al., 2005
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The onset of dorsal convergence occurs 8 hpf
Animal pole/Anterior
Dorsal
Sepich et al., 2005
mid-gastrulation (8 hpf)
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A transition in mesodermal cell behavior occurs
55 degrees from the dorsal axis
55o
90o
dorsal
dorsal
anterior
anterior
posterior
posterior
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This transition fails when noncanonical Wnt
signaling is disrupted
55o
55o
trilobite -/-
WT dnDsh
dorsal
dorsal
anterior
anterior
posterior
posterior
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Persistent directed dorsal migration involves
requires efficient cell turning
Sepich et al., 2005
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Directed migration of lateral mesodermal cells
early gastrulation
mid-gastrulation
late gastrulation
end of gastrulation
no convergence slow extension
slow convergence slow extension
slow convergence fast extension
fast convergence fast extension
cell behaviors
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105
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net dorsal speed (mm/hr)
noncanonical Wnt pathway
Jessen and Solnica-Krezel (2005)
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A noncanonical Wnt signaling pathway regulates
cell polarity underlying proper Convergence
Extension cell movements
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MT1-MMP/MMP-14 and cancer
Lynch and Matrisian (2002)
Itoh (2006)
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Wild type embryo mmp14 antisense morpholino
oligonucleotides
Wild type embryo mmp14 mRNA
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Loss of Mmp14 function disrupts Convergence
Extension cell movements -Effects on cell
polarity and adhesion?
A
B
wild type
mmp14ab MO
80 epiboly
tailbud
tailbud
80 epiboly
30o
90o
D
V
D
V
C
D
wild type - tailbud (30o)
mmp14ab MO - tailbud (30o)
E
F
H
wild type
wild type
wild type
2.5
100
mmp14ab MO
mmp14ab MO
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D
2.0
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Length-Width ratio
mediolateral alignment ( /- 20o)
G

mmp14ab MO
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82
69
1.5
25
D
1.0
0
tailbud (30o)
80 epiboly (90o)
tailbud (30o)
80 epiboly (90o)
tailbud (30o)
80 epiboly (90o)
Coyle et al., in preparation
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Epistasis experiments suggest Mmp14 interacts
with noncanonical Wnt signaling to regulate
Convergence Extension cell movements
Coyle et al., in preparation
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Directed migration of lateral mesodermal cells
Dorsal
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Directed migration of lateral mesodermal
cells Wild-type embryo injected with mmp14
morpholinos
Dorsal
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