PhD Exit Seminar – Jason Wen- Friday October 6th, 2017

PhD Exit Seminar

Friday October 6^th, 11:10 am – Ramsay Wright Building, Room 432

Jason Wen (Winklbauer lab)

“Endoderm internalization in Xenopus laevis, and the role of ephrinB1 in gastrulation”

Abstract

During animal development, the early embryo undergoes gastrulation to pattern the primary germ layers. The ancestral mode of vertebrate gastrulation can be studied using the African clawed frog Xenopus laevis. A core function of gastrulation is the movement of prospective endoderm from the surface to the embryo interior. In X. laevis, endoderm internalization is achieved through vegetal rotation, a morphogenetic process that has only been characterized at the tissue level. I have investigated the cell and molecular basis of endoderm morphogenesis in X. laevis gastrulae to connect vegetal rotation with common mechanisms of germ layer internalization in other organisms. I characterized the arrangement, shape change, and migration of cells in the endoderm and found that movement of vegetal endoderm cells located deep to the embryo surface represents an adaptation of mechanisms of epithelial internalization, particularly invagination and cell ingression, to the multilayered structure of the vegetal cell mass. Thus, this movement was termed “ingression-type migration”. Ingression-type migration integrates amoeboid-type motility, whereby cells propel forward using cell shape changes to generate locomotion, with cell tail retraction by macropinocytosis. In conjunction with differential migration — a mode of intercellular migration where cells move in a common direction but at different velocities with respect to neighbouring cells — this drives cell rearrangement during vegetal rotation. Despite their collective movement, endoderm cells are separated by vast gaps filled with extracellular material. Cells are interconnected by stitch-like contacts, and cell migration requires the adhesion molecule C-cadherin, and the matrix protein fibronectin. A basic requirement for migration is that cells must detach to complete rearrangement, and in this regard, the leading cell resolves its contact with the following cell through trailing edge retraction involving ephrinB1-dependent macropinocytosis and trans-endocytosis. Beyond the endoderm, ephrinB1 is also required for the modulation of ecto- and mesoderm tissue cohesion.