The development of the multicellular vertebrate embryo is critically dependent upon intercellular communication. In this process, a widespread mechanism is the secretion of protein signals that bind to specific membrane receptors on other cells, initiate signal transduction, affect nuclear gene activity, and alter cell fate(s). Here, we focus on signaling by Nodal (Xnr in frogs), which in embryos of all vertebrates so far studied - fish, frog, chick, mammal (including humans)- is critical for germ layer induction and patterning, and the left-right asymmetric morphogenesis and stereotyped shaping of the internal organs and cardiovascular system. The production and action of potent inducing signals must be precisely regulated, spatially and temporally, to produce the right amounts and types of embryonic tissue. A positive Nodal auto-regulatory loop, and a feedback loop involving a Nodal inhibitor Lefty/antivin that is induced by Nodal signaling, have been defined. We hypothesize that these interdependent loops provide for flexible regulation of the duration and spatial extent of nodal gene(s) expression and function in embryonic tissues. We will analyze these loops functionally and mechanistically using the experimental attributes of the frog embryo. We will: (1) Determine how """"""""Left-Right signals"""""""" are generated, transmitted, and act in the embryo. (2) Determine how Xatv modulates Nodal-mediated induction during mesoderm induction and L-R specification. (3) Characterize the processing of Xatv, and determine if differential processing of the Xatv proprotein affects its action on Xnr ligands. These studies focus on a basic inductive pathway regulating cell fate specification and coordinated morphogenesis, and to congenital defects in humans. At a cell biological level, they address the fundamental issue of how one signal affects cell fates during gastrulation, but later acts to regulate the morphogenetic behavior of overtly equivalent cell types.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Carter, Anthony D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Payne, Riley; Hoff, Henry; Roskowski, Anne et al. (2017) MICU2 Restricts Spatial Crosstalk between InsP3R and MCU Channels by Regulating Threshold and Gain of MICU1-Mediated Inhibition and Activation of MCU. Cell Rep 21:3141-3154
Halstead, Angela M; Wright, Christopher V E (2015) Disrupting Foxh1-Groucho interaction reveals robustness of nodal-based embryonic patterning. Mech Dev 136:155-65
Blum, Martin; Schweickert, Axel; Vick, Philipp et al. (2014) Symmetry breakage in the vertebrate embryo: when does it happen and how does it work? Dev Biol 393:109-23
Marjoram, Lindsay; Wright, Christopher (2011) Rapid differential transport of Nodal and Lefty on sulfated proteoglycan-rich extracellular matrix regulates left-right asymmetry in Xenopus. Development 138:475-85
Westmoreland, Joby J; Takahashi, Shuji; Wright, Christopher V E (2007) Xenopus Lefty requires proprotein cleavage but not N-linked glycosylation to inhibit nodal signaling. Dev Dyn 236:2050-61
Ohi, Yuki; Wright, Christopher V E (2007) Anteriorward shifting of asymmetric Xnr1 expression and contralateral communication in left-right specification in Xenopus. Dev Biol 301:447-63
Cha, Young Ryun; Takahashi, Shuji; Wright, Christopher V E (2006) Cooperative non-cell and cell autonomous regulation of Nodal gene expression and signaling by Lefty/Antivin and Brachyury in Xenopus. Dev Biol 290:246-64
Ripley, Anna N; Osler, Megan E; Wright, Christopher V E et al. (2006) Xbves is a regulator of epithelial movement during early Xenopus laevis development. Proc Natl Acad Sci U S A 103:614-9
Erter, C E; Wilm, T P; Basler, N et al. (2001) Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo. Development 128:3571-83
Osada, S I; Saijoh, Y; Frisch, A et al. (2000) Activin/nodal responsiveness and asymmetric expression of a Xenopus nodal-related gene converge on a FAST-regulated module in intron 1. Development 127:2503-14

Showing the most recent 10 out of 14 publications