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1 S2 Gene activity associated with the formation of mesoderm and endoderm derivatives during gastrulation Primit ive streak region Anterior : gastrula organizer (node) Mesoderm/endo derm tissues Essential gene activi ty Axial mesoderm Apc Apc NeoR Geneti c study Phenotyp i c outcome Reference Hypomorphic allele; moderate gain of WNT Abnormal axial mesoderm 34 Catnb Primitive streakspecific No axial mesoderm 35 No Foxa2-expressing tissues 6 Gdf1;Nodal Gdf1;Acv1b Compound mutant No Gsc-expressing tissues 36 Rnf111 (Akd) Knockout: Loss of No organizer-like cells 19 Smad4 Epiblast-specific Loss of prechordal plate, node and notochord 37 Foxh1 Knockout: Loss of No axial mesoderm, lacks Foxa2 and Gsc-expressing cells 20,38 Foxa2 Chimaera: null ES cells No organizer-like cells 39

2 Anterior Definitive (gut) endoderm Ctnnb1 Primitive streak specific No gut endoderm Ectopic cardiac-like mesoderm in the endoderm 35 No Cer1-expressing endoderm 6 Gdf1;Nodal Gdf1;Acv1b Compound mutant Lacks foregut endoderm 36 Smad4 Epiblast-specific Loss of definitive endoderm No effect on Mixl1 expression 37 Smad2 Mixl1 Sox17 Foxa2 Chimaera: null ES cells No contribution to gut endoderm 40,41 39,42 Paraxial mesoderm Ctnnb1 Constitutive allele due to loss of GSK3 binding site Epiblast expresses T and Snai1 Down-regulates E-cadherin 43 Tcf3 Loss of repression on WNT downstream activity Expanded Formed excess somitic mesoderm Reduced lateral plate mesoderm 44

3 Middle Paraxial mesoderm Wnt3a Knockout: Loss of Epiblast cells ingress but do not form somitic mesoderm 45 Apc Apc Min Gain of WNT Amn Transgenic insertional mutant and of the gene More paraxial mesoderm Expanded Snai1 and Eomes domain 46 Lacks paraxial mesoderm 47 Lateral plate mesoderm No Lhx1-expressing cells 6 Foxh1 Knockout: Loss of No Lefty2-expressing cells 20 Posterior Extraembryonic mesoderm Bmp4 Knockout: Loss of Lacks extraembryonic mesoderm and posterior ventral trunk mesoderm Collignon, J., Varlet, I., & Robertson, E. J. Relationship between asymmetric nodal expression and the direction of embryonic turning. Nature 381, (1996). 2. Ben Haim, N. et al. The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4. Dev Cell 11, (2006). 3. Winnier, G., Blessing, M., Labosky, P. A., & Hogan, B. L. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev. 9, (1995). 4. Rankin, C. T., Bunton, T., Lawler, A. M., & Lee, S. J. Regulation of left-right patterning in mice by growth/differentiation factor-1. Nat Genet 24, (2000). 5. Mishina, Y., Suzuki, A., Ueno, N., & Behringer, R. R. Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes Dev 9, (1995). 6. Chen, C. et al. The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo. Development 133, (2006). 7. Mishina, Y., Hanks, M. C., Miura, S., Tallquist, M. D., & Behringer, R. R. Generation of Bmpr/Alk3 mice. Genesis 32, (2002). 8. Song, J. et al. The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice. Dev Biol 213, (1999).

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