Date post: | 16-Dec-2015 |
Category: |
Documents |
Upload: | adele-charles |
View: | 216 times |
Download: | 0 times |
Vertebrate development is characterized by a series of inductive interactions
The three-signal model of mesoderm induction
Germ-layer suppression/ “Head formation”
Mesoderm formation: the 3 (or 4)-Signal Model
1-make mesoderm2-make dorsal mesoderm3-pattern mesoderm
Very useful model, although “1” likely induces mesoderm throughout the equatorial zone,and “2” and “1” act together on cells dorsally
Ventral Dorsal
Wolpert, Principles of Development (1998), Oxford Univ. Press
FGF
Signal 1=Smad2/3-mediated TGF ligand; Ras/MAPKsignaling required for maintenance
Adapted from Kimelman and Griffin (1998), Cell 94, 419-421
mesoderm induction in Xenopus
Adapted from: Massague (1998), Ann. Rev. Biochem. 67, 753-791; Hama et al. (2001), Mech. Dev. 109, 195-204.
VegT
Nodal-related ligand stimulates 2/3-type R-Smads
Signal 2: Make dorsal mesoderm
Wolpert, Principles of Development (1998), Oxford Univ. Press; Gilbert, Developmental Biology, 7th ed.(2003), Sinauer Associates, Inc.
Axial rescue
Slack (1994), Curr. Biol. 4, 116-126Wolpert, Principles of Development (1998), Oxford Univ. Press
Dorsal stabilization/nuclear localization of -catenin following cortical rotation
Gilbert, Developmental Biology, 7th ed.(2003), Sinauer Associates, Inc.;Tao et al. (2005), Cell 120, 857-871.
Molecular integration of Signal 1 and Signal 2
Gilbert, Developmental Biology, 7th ed.(2003), Sinauer Associates, Inc.
Evidence for a dorsalizing signal secreted by the Organizer
Along these same lines: dorsal recombinants dorsalize ventral explants
Signal 3: Dorsalize Mesoderm/Antagonize Ventralizers of Mesoderm
Wolpert, Principles of Development (1998), Oxford Univ. Press
BMP4 signaling ventralizes mesoderm, and is inhibited dorsally
Glinka et al. (1997) Nature 289, 517-519;Gilbert, Developmental Biology, 7th ed.(2003), Sinauer Associates, Inc.
(dorsalization via inhibition of ventralization)
Phospho-Smad1 localization
Mechanism of action of the dorsalizing, neuralizing, BMP antagonists Chordin, Noggin, and Follistatin
Wolpert, Principles of Development (1998), Oxford Univ. Press
Noggin expression
BMPs and their antagonists represent Signals 3 and 4; these factors pattern all three germ layers during gastrulation
Munoz-Sanjuan and Brivanlou (2002), Nat. Rev. Neurosci. 3, 2721-280.Gilbert, Developmental Biology, 7th ed.(2003), Sinauer Associates, Inc.Weinstein and Hemmati-Brivanlou (1997), Curr. Opin. Neurobiol. 7, 7-12.
Xbrachyury
x
xXbrachyury
Xbrachyury
Ectopic germ layer suppression: Xbrachyury promoter analysis
Modeled after: Lerchner et al. (2000), Development 127, 2729-2739.
Early gastrula Late gastrula
Ectopic germ layer suppression:“rogue cells”
Modeled after: Wardle and Smith (2004), Development 131, 4687-4696.
Mesodermal suppression by the maternal Smad4 ubiquitin ligase Ectodermin
Dupont et al. (2005), Cell 121, 87-99.
Anterior fate requires suppression of posterior (mesodermal) fate
Removal of chick hypoblast (and thus Nodal-antagonist activity),or targeted deletion of Cerl and Lefty1 in the mouse AVE gives rise to multiple primitive streaks (ectopic mesoderm).
Figures adapted from:Weinstein, D.C. (2004). In Stern, C. (ed.), Gastrulation, Cold Spring Harbor Laboratory Press, 563-570;Perea-Gomez et al. (2002), Dev. Cell 3, 745-756.
Dual inhibition of BMP and (zygotic) Wnt signaling leads to
formation of a complete secondary axis
“Head Induction”
Glinka et al. (1997) Nature 389, 517-519.
Cerberus makes extra heads only (no extra trunk)--Anti-Wnt? + Anti-BMP? + Anti-trunk inducer? Yes.
Bouwmeester et al. (1996), Nature 382, 595-601;Piccolo et al. (1999), Nature 397, 707-710
Signal 1/mesendoderm induction--Smad 2/3 + Ras/MAPK
Signal 2/dorsal axis formation--Canonical Wnt pathway, activated maternally
Signal 3/DV patterning (all germ layers)--Smad 1/5 activation/suppression
Ectodermal development--inhibit Smad 1/5, inhibit Smad 2/3,inhibit zygotic canonical Wnt signaling
Formation and patterning of the primary germ layers