Cell movements during gastrulation suggest geometry for the embryo
Frog
Chick
A
P
A
P
Frog
Chordin Chordin ChordinDorsal lip of Dorsal lip of
blastoporeblastopore
Chick
Gene expression, particularly in mesoderm, and local signaling distinguishA-P axis from early gastrulation onward in register with cell movements
…and antagonistic signaling establishes further local and axial distinctions
The geometry of cell movements during gastrulation in the mouse isdistinct, but the results are the same…
head
tail
Noggin
signal
antagonist
TF target
TF target
Germ layers are divided into anterior (head) and posterior (tail)territories by antagonistic signaling pathways that result in
local expression of transcription factor targets
Essential antagonist/agonist pairs of signals, from distinct localsources establish A-P patterning in the germ layers
Anteriorizing Posteriorizing
nogginchordin
DkkSFRPs
LeftyCerberus
The localization of antagonists in the anterior region suggeststhat “head” is a default, and “tail” must be actively constructed
Bmps
Wnts
Nodal
A schematic review of Bmp Signaling
+/+ Chord-/- Nog:Chord-/-
Loss of Bmp antagonist function disrupts head development
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 Tgf 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 signalingdecides!
Paralogues on different chromsomes:3’=anterior, 5’=posterior
There is more to posterior development than making a tail:posterior regionalization via the Hox genes
Colinear expression relies on temporally controlled chromatin remodeling in a 3’to 5’ direction
Is there a terminal posterior identity: ParaHox genes andestablishing the end of the “tail”
most posteriorly restrictedin all 3 germ layers
Head/Tail antagonismholds for RA signaling
Regulation of Hox/ParaHox expression reflects antagonist/agonist signaling
Raldh2RA synthesizingenzyme
Cyp26RA degradingenzyme
Ho
xb1
RA
Cyps
Posterior signals include Wnts, and Fgfs:establish graded gene expression in concert with RA
Hox in the head: maintaining posterior segmentation inanteriorized territory
ParaHox and Hox genes are central regulators of A-P identity
1.Conditional mutation ofCdx2 in the post-gastrulaendoderm causes posteriorgut dismorphogenesis
2a.Primary differentiated cellular characteristics of intestinal epithelium areabsent in posterior gut ofCdx2 conditional mutant
goblet cells (alcian blue)
enterocytes:alkalinephosphatase
2b. Cellular architecture is disrupted, and cell proliferation is altered in posterior gut ofCdx2 conditional mutant
3. The dysmorphogenic posterior gut has been “anteriorized” to resemble esophageal epithleium by loss of Cdx2 in post-gastrulaendoderm.
4. Anteriorization ofgut epithelium toesophageal epitheliumis accompanied byshifted expression(spatial or temporal)of anterior endodermgenes, 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
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