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Francis-West Lab

The Francis-West lab aims to understand mechanisms of skeletal development focusing on the Dchs1-Fat4 signalling pathway, which regulates cell differentiation and morphogenesis. We are also interested in understanding how mechanical signals regulate embryonic development through changes in cell fate and behaviours. The research has direct relevance to understanding human syndromes. 

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Members

Philippa Francis-West

Philippa Francis-West

Professor of Developmental and Cell Biology

project 1

Skeletal Development: Making and Shaping Bones

The aim is to understand the role of the Fat4-Dchs1 signalling pathway during mammalian development. This is an essential pathway for human development as mutations in Fat4 and Dchs1 result in Van Maldergem’s syndrome characterized by a number of developmental defects including altered craniofacial development. Fat4 and Dchs1 act together to coordinate cell polarity and growth via the Hippo pathway. Fat4 and Dchs1 mouse mutants have alterations in cell organization and proliferation which alter the development, size and shape of bones. The bones in mutants can be shorter and wider (e.g. sternum) or smaller (e.g. cranial bones). This project will investigate how Fat4 and Dchs1 control skeletal development by analysing cell shapes and organization within developing bones and the identification of transcriptional targets of Fat4-Dchs1 signalling.

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Mechanical regulation of embryonic development

In adult tissues, mechanical forces control cell behaviours such as migration, epithelial-mesenchymal transformations and Stem cell differentiation. Despite the crucial roles of mechanical forces in adult tissues, our understanding of how mechanical signals influences embryonic development is little understood. Using in vitro and in vivo model systems and Atomic Force Microscopy, the aim of this research project is to understand the role of mechanical forces, such as matrix stiffness, in the regulation of gene expression and cell differentiation during embryonic development.

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Intracellular Mechanisms of Dchs1-Fat4 signalling

Fat4 and Dchs1 act together to coordinate cell polarity and growth via the Hippo pathway. The aim of this project is to understand how Dchs1-Fat4 regulate these two very distinct cellular outcomes using in vitro and in vivo model systems. We aim to identify intracellular binding partners and transcriptional effectors of this pathway.

View all publications

The Fat4-Dchs1 pathway: A new regulator of neuronal development and migration

BBSRC - Biotechnology and Biological Sciences Research Council

Francis-West, P., Basson, A., Doherty, P.

£480,587.00

5/10/2015 → 4/3/2020

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Guest editor

Guest Editor Developmental Dynamics, Special Issue on Musculoskeletal development

Ongoing Collaboration with Dr Kenneth Irvine, Rugter’s University into the role of Dchs1-Fat4 signalling during vertebrate development

Ongoing Collaboration with Professor Andrew Pitsillides, Royal Veterinary College, London into the role of Dchs1-Fat4 signalling during skeletal development

Ongoing Collaboration with Dr Gabriel Galea, Institute of Child Health, London into the role of mechanics during neural tube closure.

Our partners

Rutger’s University, New Jersey, USA

Contact us

Professor Philippa Francis-West
Centre for Craniofacial Development & Regenerative Biology

Floor 27, Guy's Tower Wing
Guy's Hospital

0207 188 1803