All vertebrate embryos establish a basic body plan consisting of three germ layers, the ectoderm, mesoderm and endoderm, from which more complex tissues are derived. The molecular mechanism by which the basic plan is achieved is not yet clear. Recently, we have found that the maternal transcription factor VegT is an essential element in this process. We study its role by injecting antisense oligonucleotides complementary to VegT into oocytes and then fertilizing them and studying their development.
In Aim 1, we aim to understand the VegT- depleted phenotype, by examining the process of gastrulation and neurulation in its absence, and by determining how the fate map is altered in these embryos. We will answer the important question of whether VegT is directly required for both mesoderm and endoderm formation.
Aim 2 moves downstream of VegT, and asks what gene products lie downstream of VegT and can rescue the VegT-depleted phenotype.
This aim uses both a candidate gene approach and subtractive screening. It also asks whether VegT expression causes the secretion of specific growth factors.
In Aim 3, we will study the question of whether a previously described maternal signalling pathway, the dorsal pathway, which is responsible for converting mesodermal and ectodermal tissue to somites, notochord and neural tube, is still present in VegT-depleted embryos. It also turns to the question of what cell states remain when the VegT-initiated pathway and the dorsal pathway are deficient. This work will answer long-standing questions about how the body plan is set up in the early embryo, in particular providing the molecular framework for endoderm and mesoderm differentiation.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZHD1-SRC (99))
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Klein, Steven
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University of Minnesota Twin Cities
Schools of Medicine
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White, Jody A; Heasman, Janet (2008) Maternal control of pattern formation in Xenopus laevis. J Exp Zool B Mol Dev Evol 310:73-84
Mir, Adnan; Kofron, Matthew; Heasman, Janet et al. (2008) Long- and short-range signals control the dynamic expression of an animal hemisphere-specific gene in Xenopus. Dev Biol 315:161-72
Cha, J Y; Birsoy, B; Kofron, M et al. (2007) The role of FoxC1 in early Xenopus development. Dev Dyn 236:2731-41
Heasman, Janet (2006) Patterning the early Xenopus embryo. Development 133:1205-17
Birsoy, Bilge; Berg, Linnea; Williams, P Huw et al. (2005) XPACE4 is a localized pro-protein convertase required for mesoderm induction and the cleavage of specific TGFbeta proteins in Xenopus development. Development 132:591-602
Taverner, Nicola V; Kofron, Matt; Shin, Yongchol et al. (2005) Microarray-based identification of VegT targets in Xenopus. Mech Dev 122:333-54
Kofron, Matt; Puck, Helbert; Standley, Henrietta et al. (2004) New roles for FoxH1 in patterning the early embryo. Development 131:5065-78
Kofron, Matt; Wylie, Chris; Heasman, Janet (2004) The role of Mixer in patterning the early Xenopus embryo. Development 131:2431-41
Sundaram, Nambirajan; Tao, Qinghua; Wylie, Chris et al. (2003) The role of maternal CREB in early embryogenesis of Xenopus laevis. Dev Biol 261:337-52
Xanthos, Jennifer B; Kofron, Matthew; Tao, Qinghua et al. (2002) The roles of three signaling pathways in the formation and function of the Spemann Organizer. Development 129:4027-43

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