Download and posterior (tail)

Cell movements during gastrulation suggest geometry for the embryo
Frog
A
A
P
Chick
P
Gene expression, particularly in mesoderm, and local signaling distinguish
A-P axis from early gastrulation onward in register with cell movements
Chordin
Dorsal lip of
blastopore
Chordin
Chordin
Frog
…and antagonistic signaling establishes further local and axial distinctions
Chick
The geometry of cell movements during gastrulation in the mouse is
distinct, but the results are the same…
head
tail
Germ layers are divided into anterior (head) and posterior (tail)
territories by antagonistic signaling pathways that result in
local expression of transcription factor targets
antagonist
signal
TF target
Noggin
TF target
Essential antagonist/agonist pairs of signals, from distinct local
sources establish A-P patterning in the germ layers
Anteriorizing
Posteriorizing
noggin
chordin
Bmps
Dkk
SFRPs
Wnts
Lefty
Cerberus
Nodal
The localization of antagonists in the anterior region suggests
that “head” is a default, and “tail” must be actively constructed
A schematic review of Bmp Signaling
Loss of Bmp antagonist function disrupts head development
+/+
Chord-/-
Nog:Chord-/-
Multiple mechanisms can inhibit Wnt Signaling
Loss of Wnt antagonism via Dkk causes head to be
transformed into posterior tissue
Nodal signaling uses pathways similar to that for Bmp:
both are members of the Tgfb superfamily of signals
Loss of Nodal antagonism causes expansion of visceral endoderm,
normally restricted to posterior of embryo
Hex is a marker for visceral endoderm
Heads or Tails: The balance of Bmp, Wnt and Nodal signaling
decides!
There is more to posterior development than making a tail:
posterior regionalization via the Hox genes
Paralogues on different chromsomes:
3’=anterior, 5’=posterior
Colinear expression relies on temporally controlled
chromatin remodeling in a 3’to 5’ direction
Is there a terminal posterior identity: ParaHox genes and
establishing the end of the “tail”
most posteriorly restricted
in all 3 germ layers
Regulation of Hox/ParaHox expression reflects
antagonist/agonist signaling
Cyp26
RA degrading
enzyme
Hoxb1
Cyps
RA
Raldh2
RA synthesizing
enzyme
Head/Tail antagonism
holds for RA signaling
Posterior signals include Wnts, and Fgfs:
establish graded gene expression in
concert with RA
Hox in the head: maintaining posterior segmentation in
anteriorized territory
ParaHox and Hox genes are central regulators of A-P identity
1.Conditional mutation of
Cdx2 in the post-gastrula
endoderm causes posterior
gut dismorphogenesis
goblet cells (alcian blue)
2a.Primary differentiated
cellular characteristics of
intestinal epithelium are
absent in posterior gut of
Cdx2 conditional mutant
enterocytes:
alkaline
phosphatase
2b. Cellular architecture
is disrupted, and cell
proliferation is altered
in posterior gut of
Cdx2 conditional mutant
3. The dysmorphogenic posterior gut has been “anteriorized” to
resemble esophageal epithleium by loss of Cdx2 in post-gastrula
endoderm.
4. Anteriorization of
gut epithelium to
esophageal epithelium
is accompanied by
shifted expression
(spatial or temporal)
of anterior endoderm
genes, including
Hox cluster
5. Shift of expression of Wnts, transcriptional regulators,
and down stream targets (all evidence of M-E signaling in
which Wnt10a, 3a are available from M and act on E)
in anterior gut, and in posterior mutant gut