Profile

Career

2012 -	Reader	Department of Biology, University of York
2007 - 2012	Senior Lecturer	Department of Biology, University of York
1999 - 2007	Lecturer	Department of Biology, University of York
1996 - 1999	Post-doc	University of Bath
1993 - 1996	Post-doc	University of Oxford
1993	PhD	University of Virginia
1986	BSc	St Michaels College, Vermont

Research

Overview

During embryonic development, cells become committed to the skeletal muscle cell lineage and activate the expression of the myogenic regulatory genes MyoD and Myf5. These genes are dominant regulators of myogenesis and may provide a paradigm for how all cell lineages are determined. My lab is interested in how the earliest expression of the myogenic regulatory genes is activated during the development of Xenopus laevis and Xenopus tropicalis. We have shown that embryonic Fibroblast Growth Factor (eFGF), homologue of mammalian FGF4, is essential for the initial activation of MyoD (Fisher et al 2002 and Isaacs 2007). FGF ligands signal by binding receptor tyrosine kinases and this interaction requires the presence of heparan sulfate proteglycans. An enzyme called XtSulf-1 post-synthetically modifies the structure of HSPGs and by doing so influences developmental cell signals. We have shown that Sulf-1 can negatively regulated FGF signaling in frog embryos (Wang et al 2004 and Freeman et al 2008). The developmental expression of the XtSulf-1 gene is highly regulated and its protein localizes to the outside of the cell. We are investigating how the presence of Sulf-1 can influence the ability of cells in the embryos to respond to local developmental signals, including FGF, Wnt and hedgehog.

Research group(s)

Status	Name	Projects
MRC funded PhD student (2009-2013)	Simon Fellgett	Molecular and cellular analysis of Sulf1 modification of Wnt signalling in the developing frog embryo
BRSRC funded PhD student (2007-2011)	Simon Ramsbottom	The molecular analysis of Sulf1 modulation of sonic hedgehog signalling during the specification of neural precursors in the developing frog embryo
Post-Doc (BBSRC project grant 2010-2013)	Dr Richard Maguire
Senior Lab Technician	Dr Quinn

Available PhD research projects

The role of Sulf1 in modulating signals in the satellite cell stem cell niche. (for 2012-13)

In normal adult skeletal muscle there is a dedicated population of stem cells, called satellite cells, which are needed for tissue repair following injury. Satellite cells can be identified as small cells positioned between the muscle fibre and the surrounding membrane. When muscle is damaged, quiescent satellite cells are activated and re-enter the cell cycle.
This project will investigate the role of Sulf1 in modulating signals in the stem cell niche using in vivo molecular approaches in the post-genomic animal model Xenopus tropicalis. The expression of, and requirement for, Sulf1 during quiescence, proliferation and differentiation of satellite cells will be investigated.

Publications

Selected publications

Winterbottom, EF  and  Pownall, ME.  Complementary expression of HSPG 6-O-endosulfatases and 6-O-sulfotransferase in the hindbrain of Xenopus laevis Gene Exp Patterns 9 2009 166-72

Branney, PA., Faas, L,  Steane, SE, Pownall, ME and Isaacs HV. Characterisation of the fibroblast growth factor dependent transcriptome in early development. PLoS One. 2009;4(3):e4951

Guiral EC, Faas L, Pownall ME. .Neural crest migration requires the activity of the extracellular sulphatases XtSulf1 and XtSulf2. Developmental Biology 341(2) 2010 375-88

Pownall, ME and Isaacs, HV  FGF Signalling in Vertebrate Development Colloquium Series on Developmental Biology, 1 (1)  2010  1-75
 

Fisher ME, Isaacs HV and Pownall ME (2002) eFGF is required for the activation of XmyoD in the myogenic cell lineage of Xenopus laevis Development 129: 1307-1315

Wang S, Ai X, Freeman SD, Pownall ME, Lu Q, Kessler DS and Emerson CP (2004) QSulf1, a heparan sulfate 6-O endosulfatase, inhibits FGF-induced mesoderm formation and angiogenesis by modulating FGF ligand -receptor interaction PNAS 101: 4833-38

Freeman SD, Moore WM, Guiral EC, Holme A, Turnbull JE and Pownall ME (2008) Extracellular regulation of developmental cell signalling by XtSulf1 Developmental Biology 320(2): 436-45

Isaacs HV, Deconinck AE and Pownall ME (2007) FGF4 regulates blood and muscle specification in Xenopus laevis Biology of the Cell 99(3): 165-73

External activities

Memberships

• Member of the British Society for Developmental Biology committee

Editorial duties

• Editorial review boards: Biology of the Cell