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Terry P. Yamaguchi, Ph.D.

Gallery Pictures

Establishment of the anterior-posterior (AP) axis and gastrulation in the mouse embryo.
Establishment of the anterior-posterior (AP) axis and gastrulation in the mouse embryo.
The dashed line overlying the 5.5 dpc embryo indicates the junction between extraembryonic and embryonic ectoderm (epiblast) cells (orange). The epiblast alone gives rise to all cells of the embryo proper. The extraembryonic regions of 6.0-7.5 dpc embryos are outlined for clarity. Prior to gastrulation (before 6.5 dpc), visceral endoderm (VE) cells underly the adjacent embryonic ectoderm (epiblast) in the distal end of the conceptus. VE cells are extraembryonic and do not directly contribute cells to the embryo. Distal visceral endoderm (DVE) cells move anteriorly (arrow) to form the anterior visceral endoderm (AVE) by 6.0 dpc, where they function to anteriorize the adjacent presumptive neural plate (blue). Gastrulation begins at 6.5 dpc with the formation of the primitive streak (PS, red dots) at the posterior end of the embryo. The curved line indicates the proximal-distal length of the primitive streak, which increases as gastrulation proceeds. Mesoderm (red), definitive endoderm (brown), and axial mesendoderm (black) precursors arise in the streak by 7.0 dpc and undergo coordinated morphogenetic movements (arrows) that leads to their eventual placement in anterior positions. Mesoderm cells move immediately adjacent to the overlying epiblast, while definitive endoderm cells constitute the outer-most layer of the conceptus. Anterior and proximal movement of definitive endoderm cells displaces visceral endoderm to extraembryonic locations. Mesodermal cells arising in the anterior end of the primitive streak at 7.0 dpc are presumptive heart mesoderm (red-green hatching), and move to the anterior-most embryonic region by 7.5 dpc where they will form the heart (green). Anterior definitive endoderm (ADE; pink) gives rise to foregut, while the anterior neural plate (blue) forms the forebrain (Curr Biol 11: R713-24, 2001).
A diverse set of proteins modulate the canonical Wnt/beta-catenin signaling pathway.
A diverse set of proteins modulate the canonical Wnt/beta-catenin signaling pathway.
The transcriptional coactivator beta-catenin is the primary effector of this pathway. A hypothetical anterior embryonic cell is depicted on the left, while a posterior cell is on the right. For the sake of simplicity, most components are illustrated as being expressed equivalently in anterior and posterior cells. (Left) In anterior regions of the embryo, the abundant secreted Wnt inhibitors sFRP and Cerberus (Cer) bind Wnts directly (although not necessarily mutually exclusively) to prevent their interaction with Frizzled (Fz) receptors. The secreted Wnt inhibitor Dkk1 binds directly to LRP6 to inhibit its function as a Wnt co-receptor. In the absence of a functional Wnt/Fz/LRP membrane complex, beta-catenin (beta-cat) resides in a cytoplasmic multiprotein complex containing the serine/threonine kinase GSK3beta, the tumor suppressor APC, and the scaffolding protein Axin. Phosphorylation of APC by GSK3beta promotes binding of APC to beta-catenin which, in turn, promotes binding of beta-catenin to Axin. Beta-catenin phosphorylation by GSK3beta leads to ubiquitination and consequent degradation by the proteasome. The DNA-binding TCF (T cell factor) proteins are context-dependent transcription factors, acting as repressors of Wnt target genes by association with negative transcriptional regulators such as Groucho (Grg) in the absence of a Wnt signal. (Right) The binding of abundant posteriorly expressed Wnts to Fz and LRP6 is facilitated by heparan sulfate proteoglycans (HSPG). LRP5 recruits the multiprotein Axin complex to the membrane by direct binding to Axin. Dishevelled (Dvl) binds Axin and the GSK3beta binding protein GBP. GBP inhibits Axin-bound GSK3beta activity. Inhibition of GSK3beta leads to hypophosphorylation of both APC and beta-catenin leading to the release of beta-catenin from the complex and blocking its degradation. Elevated levels of stabilized beta-catenin translocate to the nucleus and bind to TCF proteins, acting as coactivators of TCFs to stimulate transcription of Wnt target genes (Curr Biol 11: R713-24, 2001).
Mouse Node/organizer
Mouse Node/organizer
Confocal microscopy image of ciliated ventral node epithelial cells in a 2 somite stage (embryonic day 8.5) embryo. The node, or organizer, is an important signaling center during vertebrate development that controls the formation of the Left-Right body axis. Anti-acetylated tubulin stains the cilia (green) found on the apical surface of epithelial cells of the node. The cilia play an essential role in establishing the Left-Right axis but the mechanism remains unknown. Actin filaments (red) are visualized with fluorescently labeled phalloidin, and nuclei (blue) are stained with TOPRO-3.
The Yamaguchi Lab, 2004
The Yamaguchi Lab, 2004
L-R: Tadasuke Tsukiyama, Jaime Greear, Bowlathon trophy, Masa-aki Nakaya, Chizuru Nakaya, Terry Yamaguchi, Kristin Biris, Bill Dunty
The Annual Yamaguchi/Lewandoski Bowlathon
The Annual Yamaguchi/Lewandoski Bowlathon
Christmas, 2003
The Yamaguchi Lab emerges victorius once again!
Happy Yamaguchi Lab, Summer 2005
Happy Yamaguchi Lab, Summer 2005
L-R: Jaime Greear, Masa-aki Nakaya, Garrett Dunty, Erynn Layman, Bill Dunty, Kristin Biris, Evan, Logan and Terry Yamaguchi

This page was last updated on 2/4/2008.