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Localized
determinants and
asymmetric cell
divisions establish
the body plan of the
early embryo
Body axes:
1) Animal-vegetal
2) Dorsal-ventral
3) Anterior-posterior
4) Left-right
Gastrulation
and
neurulation
in the frog
embryo
Development of the nervous system from the gastrula
Formation of the notochord and neural tube
BMPs, Wnt
in neural plate
ectoderm
Shh secreted
from notochord
& floor plate
Neural tube
closure triggers
neural crest
delamination
*No neural induction
w/o competence conferred
by mesoderm
*Neural induction occurs
because of signaling from
mesoderm
What is an “organizer”?
Spemann and Mangold
implicate the dorsal lip
of the blastopore in
neural induction
Neural fate is suppressed by contact-mediated inhibition in
ectoderm
BMP signaling (TGF-beta superfamily)
Nature Reviews Rheumatology 6, 518-527 (September 2010)
TGF-beta superfamily of signal transduction
Blocking TGF-beta like
signaling causes animal
cap tissue to become
neural
Secreted ligand BMP4
suppresses neural fate in
ectoderm
no Ca2+
Mesoderm induction in frog embryos: A + V = M
(or Ec + En = M)
Neural induction
Dorsalizing Xenopus embryo: activates Noggin to suppress BMP signaling
= neural fate
Noggin, Chordin:
Neural inducers
UV blocks
cortical
rotation;
Li+ blocks PI
signaling/
increases
chordin via
gsc
Sperm entry point induces cortical rotation to induce dorsal organizer
(vegetal cx + animal cytoplasm)
… and: animal cx + vegetal cytoplasm = ventral
Chordin: in the right place at the right time…
Chordin
injection
Secondary axis 
wt
Noggin -/-
Noggin -/-; Chordin -/-
Mechanics of the organizer and gastrulation in frog
Cerberus, Chordin,
Noggin, Follistatin
(meso/endo)
vs.
BMPR & BMP4
(ectodermal)
Fgfr & Fgf8 (neural)
The epidermal-neural switch: BMP off + FGF on
Zic1/Zic3
required
for neural
plate
In Drosophila, ventral nerve cord derives from condensed
neurons & glia
In flies, dpp= BMP
(blocks neural), &
sog= noggin/chordin
(promotes neural)
Position of cells determines
level of exposure to
morphogen  what the cell
will be when it grows up
Morphogens drive differential gene expression
Cells acquire positional information in the limb bud
Fgf8 = blue (AER)
Shh = red (polarizing region)
Yellow = proliferating progenitors
Shh
in the
polarizing
region
Grafting of ectopic polarizing region causes digit duplication
Restriction of Gene Expression
Transcription factor “zip code” sets the map of positions where
motor neurons or interneuron subtypes will differentiate
Opposing morphogen gradients pattern the D-V axis of the
spinal cord
Dorsal neural
tube: BMP4
Ventral neural
tube & notochord:
Shh
Motor neuron differentiation depends on Shh and the notochord
Levels of the diffusible morphogen Shh pattern the neural tube:
low = dorsal (Pax 7)
medium = middle (Olig2)
high = ventral (Nkx2.2)
Neural tube
dissections:
Increasing BMP4
levels leads to
dorsal fate
specification, even
in the presence of
Shh
(Liem et al, 1995)
Ectoderm =
source of BMP4;
turns on TFs
Msx1/2, HNK1,
slug
Dorsal ectoderm, then dorsal neural tube cells express BMPs;
ventral notochord then ventral floorplate expresses Shh