Professor Marysia Placzek
Professor in Developmental Neurobiology
Room: D18b Firth Court
Brief career history
We study how the hypothalamus of the brain is formed in the embryo
In development, hypothalamic nerves and glia are built in space and time with an order and precision that leads ultimately to the integrated assembly of the brain-body axis. The proper development of the hypothalamus is therefore vital to ensure that throughout life, brain and body function in perfect harmony and balance. Our research focuses on the stem and progenitor cells that build the hypothalamus. Our goal is to characterise the molecular networks involved in hypothalamic development, and determine how they work to build and maintain the different cells of the hypothalamus. Our work will contribute to understanding the importance of the hypothalamus to robust long-term health and will shed light onto diseases and disruptions of homeostasis.
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 hypothalamic cells form in development. This knowledge is important, because early indications suggest that deregulation of developmental programmes may underlie complex human pathological conditions, including stress and eating disorders. Our goal is therefore to understand how the hypothalamus develops in the embryo and how the proper embryonic assembly of the hypothalamus holds the key to robust adult function. We focus in particular on five key areas:
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.
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:
- Fu T, Towers M & Placzek M (2017) Fgf10(+) progenitors give rise to the chick hypothalamus by rostral and caudal growth and differentiation.. Development. View this article in WRRO
- 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.