Professor Marysia Placzek
Professor in Developmental Neurobiology
Room: D18b Firth Court
Brief career history
A major focus of our research is to understand the development of the vertebrate hypothalamus. We are aiming to characterise the signalling factor/transcription factor networks that mediate hypothalamic development, elucidate how hypothalamic stem cells progress into defined neuronal cells and how their axons project to different components of the hypothalamus. A second focus is the elucidation of the signalling factor/transcriptional networks that underlie development of the prechordal mesoderm.
Building the hypothalamus through life
My research focuses on the development of the hypothalamus and on its cellular plasticity over the lifecourse. The functions of the hypothalamus in mediating homeostasis are well-known. By contrast, little is understood of how its resident cells form in development, or through life. This knowledge is important, because early indications suggest that deregulation of developmental programmes may underlie complex human pathological conditions, including stress and eating disorders. We use a range of animal model systems (chick, mouse, zebrafish) and combine in vivo and ex vivo approaches with imaging, transgenic, gain-and loss-of-function approaches to characterise how stem/progenitor cells renew, or differentiate in response to local and systemic signals.
Recent work has focused on FGF signalling, showing its importance in building brain-body interfaces (1) and in the proliferation of resident stem/progenitor cells in the embryo (2) and adult (3). Currently we are examining other signalling pathways that promote differentiation, and collaborating with Towers to address the role of cell cycle in hypothalamic morphogenesis. With Furley, we are further characterising hypothalamic neural stem/progenitor cells and the local factors, including cell adhesion molecules, that govern their behaviour.
A role for glucocorticoids in stimulating neurogenesis from adult hypothalamic stem cells (3) is being investigated with Taylor (University of Basel), while with Cunliffe, Watt and Wood (UoS) we ask whether alterations in hypothalamic stem/progenitor cell behaviour underlie pathological conditions. In collaboration with Lovell-Badge (Crick Institute, Mill Hill) we are examining if hypothalamic stem cells decline in ageing, with consequences on neuronal depletion.
Undergraduate and postgraduate taught modules
Postgraduate PhD project
Functional characterisation of stem cell-derived neural progenitors in the central nervous system
Co-supervisor: Dr Anestis Tsakiridis
Human pluripotent stem cells (hPSCs) are a valuable source of clinically relevant cell populations such as neural progenitors and neurons (Suzuki and Vanderhaeghen, 2015). However, conventional differentiation protocols produce predominantly neural cell types corresponding to the anterior central nervous system (CNS) such as the brain and anterior (cervical) spinal cord but fail to generate efficiently more posterior (thoracic/lumbosacral) spinal cord cells. In vivo, the anterior-posterior (A-P) identity of various CNS cell types has been shown to influence both their function and their susceptibility to neurodegeneration e.g. in the case of Amyotrophic lateral sclerosis (ALS).
Currently it is unknown whether such differences exist in in vitro-derived neural cells and whether the predominantly anterior CNS cell types generated from hPSCs are functionally equivalent to their posterior counterparts. This is an important issue for the design of drug screening/disease modelling experiments as well as cell replacement-based therapies that employ neural derivatives of hPSCs. We have recently described the in vitro generation of neuromesodermal progenitors (NMPs), the bona fide early precursors of spinal cord in vertebrate embryos, from hPSCs (Henrique et al. 2015; Gouti et al., 2015). Using NMPs as the starting population we have now established pilot protocols driving the robust induction of posterior spinal cord progenitors and neurons in vitro.
The proposed PhD project combines expertise in the Tsakiridis and Placzek labs in the derivation and manipulation of stem cells (Gouti et al. 2015; Robins et al. 2013) and aims to examine whether posterior CNS cells “behave” in the same way as their anterior counterparts in terms of:
1) Vulnerability to excitotoxicity/cellular stress
The project will employ a variety of experimental approaches such as hPSC culture and differentiation, high content imaging and chick embryo manipulation.
1) Suzuki IK and Vanderhaeghen P Development. 2015 Sep 15;142(18):3138-50).
For further information about this project and how to apply, see our PhD Opportunities page:
- Eachus H, Bright C, Cunliffe VT, Placzek M, Wood JD & Watt PJ (2017) Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function. Human Molecular Genetics, 26(11), 1992-2005. View this article in WRRO
- Muthu V, Eachus H, Ellis P, Brown S & Placzek M (2016) Rx3 and Shh direct anisotropic growth and specification in the zebrafish tuberal/anterior hypothalamus. Development, 143, 2651-2663. View this article in WRRO
- Burbridge S, Stewart I & Placzek M (2016) Development of the Neuroendocrine Hypothalamus.. Compr Physiol, 6(2), 623-643.
- Ellis PS, Burbridge S, Soubes S, Ohyama K, Ben-Haim N, Chen C, Dale K, Shen MM, Constam D & Placzek M (2015) ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm. Development, 142(22), 3821-3832. View this article in WRRO
- Robins SC, Stewart I, McNay DE, Taylor V, Giachino C, Goetz M, Ninkovic J, Briancon N, Maratos-Flier E, Flier JS, Kokoeva MV & Placzek M (2013) α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors.. Nat Commun, 4, 2049. View this article in WRRO
- Liu F, Pogoda H-M, Pearson CA, Ohyama K, Löhr H, Hammerschmidt M & Placzek M (2013) Direct and indirect roles of Fgf3 and Fgf10 in innervation and vascularisation of the vertebrate hypothalamic neurohypophysis.. Development, 140(5), 1111-1122.