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.

Members

Philippa Francis-West

Professor of Developmental and Cell Biology

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.

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.

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.

Dchs1-fat4 regulation of osteogenic differentiation in mouse
Crespo-Enriquez, I., Hodgson, T., Zakaria, S., Cadoni, E., Shah, M., Allen, S., Al-Khishali, A., Mao, Y., Yiu, A., Petzold, J., Villagomez-Olea, G., Pitsillides, A. A., Irvine, K. D. & Francis-West, P., Jul 2019, In : Development (Cambridge). 146, 14, dev176776 . Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1242/dev.176776
Mechanics of development
Nowlan, N. C., Francis-West, P. & Nelson, C., 1 Jan 2018, In : Philosophical Transactions of the Royal Society B: Biological Sciences. 373, 1759, 20170316. Research output: Contribution to journal - Editorial. DOIs: https://doi.org/10.1098/rstb.2017.0316
Altered Neocortical Gene Expression, Brain Overgrowth and Functional Over-Connectivity in Chd8 Haploinsufficient Mice
Suetterlin, P., Hurley, S., Mohan, C., Riegman, K. L. H., Pagani, M., Caruso, A., Ellegood, J., Galbusera, A., Crespo-Enriquez, I., Michetti, C., Yee, Y., Ellingford, R., Brock, O., Delogu, A., Francis-West, P., Lerch, J. P., Scattoni, M. L., Gozzi, A., Fernandes, C. & Basson, M. A., 1 Jun 2018, In : Cerebral Cortex. 28, 6, p. 2192-2206 Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1093/cercor/bhy058
Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization during Lymphatic Valve Morphogenesis - Brief Report
Pujol, F., Hodgson, T., Martinez-Corral, I., Prats, A. C., Devenport, D., Takeichi, M., Genot, E., MÃ¤kinen, T., Francis-West, P., Garmy-Susini, B. & Tatin, F., 1 Sep 2017, In : Arteriosclerosis, Thrombosis, and Vascular Biology. 37, 9, p. 1732-1735 4 p. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1161/ATVBAHA.117.309818
Active GSK3Î² and an intact Î²-catenin TCF complex are essential for the differentiation of human myogenic progenitor cells
Agley, C. C., Lewis, F. C., Jaka, O., Lazarus, N. R., Velloso, C., Francis-West, P., Ellison-Hughes, G. M. & Harridge, S. D. R., 1 Dec 2017, In : Scientific Reports. 7, 1, 13189. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1038/s41598-017-10731-1https://doi.org/10.1038/s41598-017-10731-1
Mechanoregulation of neural crest cell fate: 18th International Congress of Developmental Biology 18-22 June, University Cultural Centre, National University of Singapore
Dawson, M., de Sousa, C. F., Crespo-Enriquez, I., Hodgson, T., Gentleman, E. & Francis-West, P., Jul 2017, In : Mechanisms of Development. 145, Supplement, p. S43 Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1016/j.mod.2017.04.069
Deficiency and also transgenic overexpression of Timp-3 both lead to compromised bone mass and architecture in vivo
Javaheri, B., Hopkinson, M., Poulet, B., Pollard, A. S., Shefelbine, S. J., Chang, Y. M., Francis-West, P., Bou-Gharios, G. & Pitsillides, A. A., 12 Aug 2016, In : PL o S One . 11, 8, e0159657. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1371/journal.pone.0159657
BMP signaling regulates the fate of chondro-osteoprogenitor cells in facial mesenchyme in a stage-specific manner: BMP Levels Regulate Facial Chondrogenic Condensations
Celá, P., Buchtová, M., Veselá, I., Fu, K., Bogardi, J., Song, Y., Barlow, A., Buxton, P., Medalová, J., Francis-west, P. & Richman, J. M., 25 Jul 2016, In : Developmental Dynamics. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1002/dvdy.24422
Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae
Kuta, A., Mao, Y., Martin, T., de Sousa, C. F., Whiting, D., Zakaria, S., Crespo-Enriquez, I., Evans, P., Balczerski, B., Mankoo, B., Irvine, K. D. & Francis-West, P., Jul 2016, In : Development (Cambridge): for advances in developmental biology and stem cells. 143, 13, p. 2367-2375 9 p. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1242/dev.131037
Dchs1-Fat4 regulation of polarized cell behaviours during skeletal morphogenesis
Mao, Y., Kuta, A., Crespo-Enriquez, I., Whiting, D., Martin, T., Mulvaney, J., Irvine, K. D. & Francis-West, P., 5 May 2016, In : Nature Communications. 7, 11469. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1038/ncomms11469

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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

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

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

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

0207 188 1803

Philippa.francis-west@kcl.ac.uk

Francis-West Lab

Members

Philippa Francis-West

Skeletal Development: Making and Shaping Bones

Mechanical regulation of embryonic development

Intracellular Mechanisms of Dchs1-Fat4 signalling

Dchs1-fat4 regulation of osteogenic differentiation in mouse

Mechanics of development

Altered Neocortical Gene Expression, Brain Overgrowth and Functional Over-Connectivity in Chd8 Haploinsufficient Mice

Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization during Lymphatic Valve Morphogenesis - Brief Report

Active GSK3Î² and an intact Î²-catenin TCF complex are essential for the differentiation of human myogenic progenitor cells

Mechanoregulation of neural crest cell fate: 18th International Congress of Developmental Biology 18-22 June, University Cultural Centre, National University of Singapore

Deficiency and also transgenic overexpression of Timp-3 both lead to compromised bone mass and architecture in vivo

BMP signaling regulates the fate of chondro-osteoprogenitor cells in facial mesenchyme in a stage-specific manner: BMP Levels Regulate Facial Chondrogenic Condensations

Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae

Dchs1-Fat4 regulation of polarized cell behaviours during skeletal morphogenesis

Guest editor

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Francis-West Lab

Members

Skeletal Development: Making and Shaping Bones

Mechanical regulation of embryonic development

Intracellular Mechanisms of Dchs1-Fat4 signalling

Guest editor

Our partners

Contact us

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