CRM External Seminar: Dr Derk ten Berge, Group Leader, Cell Biology, Erasmus MC, The Netherlands

Dr Derk ten Berge

Department of Cell Biology, Erasmus MC, University Medical Center Rotterdam, the Netherlands

Contact details

Talk title

Pluripotency transitions, morphogenesis, and the modular control of embryonic self-organisation

Host

Ian Chambers

Abstract

Mammalian embryogenesis seems to unfold by the purposeful guidance of obedient cells. Yet each cell makes its own decisions, responding to its environment with no plan or purpose. How these individual responses organise cells into tissues and organs remains poorly understood for even the simplest embryonic stages. All mammalian embryos originate from the epiblast, a sheet of pluripotent cells that forms prior to gastrulation. In mouse, epiblast precursors are specified in the pre-implantation embryo in a state of naive pluripotency. Following implantation, these differentiate into their mature state of primed pluripotency. Meanwhile, the cells gain apicobasal polarity and arrange into a rosette, followed by the opening of a lumen in its center which converts the epiblast into its mature monolayer epithelial morphology. Derk's group investigated how epiblast differentiation and morphogenesis are coordinated and synchronised with the extraembryonic tissues, using embryos and various embryo models. Importantly, we identified an intermediate rosette pluripotent state, dissecting epiblast differentiation into distinct naïve-rosette and rosette-primed pluripotency transitions that coincide with rosette formation and lumenogenesis, respectively. Moreover, a single signal, WNT or FGF/MEK respectively, controls not only differentiation but also morphogenesis during these transitions. Surprisingly, they found that downstream effectors control separate differentiation and morphogenesis modules that act independently and are responsive to additional inputs and feedback, including from extraembryonic tissues. These tissue interactions synchronize epiblast and extra-embryonic development by arresting them at a defined stage, while subsequent development is promoted by repeated interactions that reinforce differentiation and morphogenesis. The group's findings point to a highly responsive and unexpectedly flexible network of differentiation and morphogenesis modules that coordinates and synchronises development, both within and between tissues. 

Bio

Derk ten Berge is a group leader at the Erasmus Medical Center in Rotterdam (since 2009). He earned an MSc degree in chemistry at Utrecht University and a PhD in mouse molecular genetics at the Hubrecht Institute for Developmental Biology, both in Utrecht, the Netherlands. In 2000 he moved to the lab of Roel Nusse at Stanford University for his postdoc. His research focuses on mechanisms of embryonic self-organisation, in particular the role of tissue interactions, and involved limb development, gastrulation and pre-implantation development using mouse, chick and human embryos. He pioneered the use of stem cells to model embryonic development. In 2008, he revealed the first 3D model of gastrulation, demonstrating the surprising self-organising abilities of embryonic stem cells and kicking off the current boom in embryo models. He identified important roles for WNT signals in regulating pluripotency and differentiation of mouse and human embryonic stem cells. Recently, he demonstrated a series of pluripotency transitions during pregastrulation development, coupled to morphogenetic events and regulated by interactions between embryonic and extra-embryonic tissues. These findings point to a flexible network of differentiation and morphogenesis modules that mediates embryonic self-organization and is highly adaptive and responsive to developmental disturbances.