Scholpp Group


Contact-mediated signalling in development and disease

Group Members

Group LeaderPostdoctoral ResearchersPhD StudentsResearch Technicians
Steffen ScholppLucy Brunt
Yosuke Ono
Tom Piers
Sally Rogers
Michael Dawes
Kevin Fang
Daniel Routledge
Gemma Sutton
Chengting Zhang
Agnieszka Kaczmar

Cell-to-cell communication is essential for regulating the development of all multicellular organisms. Intercellular communication is based on chemical stimuli – including signalling proteins – which control the cellular behaviour in a tissue. An important family of signalling proteins that orchestrate development is the Wnt signalling family. Wnts regulate vital cellular processes, including how fast cells divide; the fate of cells or how to differentiate into different forms; and how cells move. Wnt signalling is therefore fundamental to the development of early life (e.g. embryogenesis), and organ development, but also during tissue homeostasis and thus crucial during wound healing and regeneration. Furthermore, we know that a relatively small and specific group of cells control and distribute Wnt proteins controlling development. Adjacent, larger groups of cells then respond to the signal. Wnt function is therefore dependent on the precise delivery of Wnt proteins from producing cells to responding cells.

Currently, how Wnt proteins are transported between cells to activate signalling is unknown. As such, we do not understand how the message is delivered from one cell to another. Our research aims to understand how the message is conveyed between cells.  Our research has revealed the existence of a completely unexpected cell-to-cell transport mechanism for Wnt proteins. Specific finger-like cell membrane protrusions – called cytonemes – carry Wnt proteins and transport them to neighbouring cells. After contact with the target cell, Wnt proteins are taken up by the responding cells. This process leads to signal activation in a target cell. Impairment of the number of Wnt protein transported on these signal protrusions leads to severe consequences during development, leading to malformation of tissues and severe developmental difficulties. Understanding the systems that govern this newly identified transport system is, therefore, fundamental for understanding how Wnt functions during embryogenesis and tissue homeostasis.

Alumni

Dr Benjamin Matthes

Dr Joana Viana

Jenna Corcoran

Holly Elson

Simone Schindler

Collaborators

Prof Robert Kelsh, U Bath

Toby Phesse, PhD, Cardiff U

Prof Trevor Dale, Cardiff U

Prof David Virshup, Duke-NUS

Prof Selina Wray, UCL

Prof Katie Lunnon, CMH Exeter

Prof Melissa Fishel, IU, US

Prof Paul Martin, Bristol