Cell movements during gastrulation suggest geometry for the embryo

1. Frog A A P P Chick Cell movements during gastrulation suggest geometry for the embryo

2. Chordin Chordin Chordin Dorsal lip of blastopore Frog Chick Gene expression, particularly in mesoderm, and local signaling distinguish A-P axis from early gastrulation onward in register with cell movements …and antagonistic signaling establishes further local and axial distinctions

3. head tail The geometry of cell movements during gastrulation in the mouse is distinct, but the results are the same…

4. antagonist signal TF target Noggin 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

5. noggin Bmps chordin Dkk SFRPs Wnts Lefty Cerberus Nodal Essential antagonist/agonist pairs of signals, from distinct local sources establish A-P patterning in the germ layers Anteriorizing Posteriorizing The localization of antagonists in the anterior region suggests that “head” is a default, and “tail” must be actively constructed

6. A schematic review of Bmp Signaling

7. +/+ Nog:Chord-/- Chord-/- Loss of Bmp antagonist function disrupts head development

8. Multiple mechanisms can inhibit Wnt Signaling

9. Loss of Wnt antagonism via Dkk causes head to be transformed into posterior tissue

10. Nodal signaling uses pathways similar to that for Bmp: both are members of the Tgfb superfamily of signals

11. Hex is a marker for visceral endoderm Loss of Nodal antagonism causes expansion of visceral endoderm, normally restricted to posterior of embryo

12. Heads or Tails: The balance of Bmp, Wnt and Nodal signaling decides!

13. 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 Paralogues on different chromsomes: 3’=anterior, 5’=posterior

14. most posteriorly restricted in all 3 germ layers Is there a terminal posterior identity: ParaHox genes and establishing the end of the “tail”

15. Cyp26 RA degrading enzyme Cyps Hoxb1 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 Regulation of Hox/ParaHox expression reflects antagonist/agonist signaling

16. Hox in the head: maintaining posterior segmentation in anteriorized territory

17. ParaHox and Hox genes are central regulators of A-P identity

19. 1.Conditional mutation of Cdx2 in the post-gastrula endoderm causes posterior gut dismorphogenesis

20. goblet cells (alcian blue) 2a.Primary differentiated cellular characteristics of intestinal epithelium are absent in posterior gut of Cdx2 conditional mutant enterocytes: alkaline phosphatase

21. 2b. Cellular architecture is disrupted, and cell proliferation is altered in posterior gut of Cdx2 conditional mutant

22. 3. The dysmorphogenic posterior gut has been “anteriorized” to resemble esophageal epithleium by loss of Cdx2 in post-gastrula endoderm.

23. 4. Anteriorization of gut epithelium to esophageal epithelium is accompanied by shifted expression (spatial or temporal) of anterior endoderm genes, including Hox cluster

24. 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