Professor Betsy Pownall 

Research

Embryonic development orchestrates the proliferation and differentiation of many hundreds of cell types that will interact to form tissues, underpinning organ and organismal function. It is essential to understand the normal processes that regulate the remarkable achievement of embryogenesis in order to have the knowledge necessary to harness the potential of stem cells and gene editing to develop new therapeutics to benefit society. We use non-mammalian vertebrate embryos to study developmental mechanisms. The models used in our labs are Xenopus laevis and tropicalis and the zebra fish, Danio rerio.

Differential gene expression drives the establishment of distinct cell lineages during development and the regulation of protein coding genes has been widely studied. For instance, the establishment of the myogenic cell lineage requires a set of bHLH transcription factors known collectively as myogenic regulatory factors (MRFs) that include myoD, myf5, myogenin, and MRF4 (reviewed in Pownall et al, 2002). These factors are central to a gene regulatory network (GRN) that promotes proliferation of a progenitor population with myogenic potential and later activates the coordinated transcription of genes that code for contractile protein. My lab has defined a role for FGF signalling in the early activation of MyoD in gastrula stages of Xenopus development (Fisher et al, 2002; Burks et al 2009) and we have used transcriptomics to identify the targets of MyoD at this early stage of muscle specification (Maguire et al, 2012, McQueen and Pownall , 2017) continuing our investigation into the signals and transcriptional hierarchies that regulate skeletal muscle development.

Heparan sulfate proteoglycans (HSPGs) are important regulators of FGF signalling and can be structurally modified by the extracellular 6-O-endosulfatase, Sulf1. My lab has helped to demonstrate that Sulf1 is a potent negative regulator of FGF signalling (Wang et al., 2004; Freeman et al., 2008) and that Sulf1 also impacts other signalling pathways that require HSPGs, such as Shh, BMP and Wnt (Ramsbottom et al, 2014, Meyers et al, 2013, and Fellgett et al, 2015) where it acts to influence diffusion of ligands and shape gradients. A BBSRC funded collaboration with Prof Stefan Hoppler (Aberdeen) and Prof Masanori Taira (Tokyo) interrogates how feedback of Wnt signalling can modify ligand diffusion.

Research group

• Caitlin McQueen, PhD student, ‘Transcriptional regulation of myogenesis’
• Gideon Hughes, PhD student, ‘Modelling Parkinson’s Disease in zebrafish’
• Lewis White, PhD student, ‘Adaptations in Alcolapia’