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Professor Marysia Placzek

Director: Basic Science

Marysia Placzek obtained a B.Sc. in Molecular Biology from Edinburgh University, UK, in 1982 and then pursued Ph.D. research on mammary tumour development in Gordon Peter’s laboratory at Imperial Cancer Research Fund, London (CRUK). She performed postdoctoral training with Jane Dodd at Columbia University, New York, working on the differentiation and functional role of floor plate cells of the vertebrate spinal cord. On returning to the UK in 1992 to set up her independent lab at the National Institute for Medical Research, London, she furthered studies on the floor plate and axial mesoderm. Marysia moved to the department of Biomedical Science at the University of Sheffield in 1997, and was appointed to a personal Chair in 1999, heading the laboratory of Developmental Neurobiology. Current research interests include the molecular mechanisms of hypothalamic differentiation and the specification of ventral midline fates within the vertebrate neural tube.

Research

Summary for nonspecialist

Nerve cells in a small region of the ventral forebrain, the hypothalamus, direct processes towards the underlying pituitary gland. Together, hypothalamic nerves and cells in the pituitary are responsible for maintaining body homeostasis. Despite the importance of the hypothalamic nerves, we know very little about how they form, or how their processes grow towards the pituitary. We are performing experiments that address these questions: if we can understand how hypothalamic nerves are born and grow then we can hope to understand how they go wrong in disease and disorders.

Image 1. Immunofluorescence showing ventral midline structures in the chick embryonic CNS.

Technical Summary

The development of the nervous system in vertebrate embryos is intriguing and fascinating. The brain and spinal cord form from a tube of neural cells that form early in embryogenesis – the neural tube. Directed patterning events transform the neural tube into the brain and spinal cord, and into the many different neural cell types that form in these two structures.

An intricate network of neural connections then develops, establishing the foundation of the mature, functioning nervous system.

Image 2. Double colour in situ hybridisation showing Tbx2 expression in the ventral hypothalamus (blue) and Sonic hedgehog expression (red).

We are especially interested in the development and role of cells that form at the ventral midline of the neural tube. In the spinal cord, these cells are termed the floor plate. They govern the patterning of the adjacent neural tube - first through their secretion of Sonic hedgehog - a protein that governs neuronal identity in adjacent cells, and then through expression of proteins that act to guide developing axons. In the forebrain, ventral midline cells take on a different fate - that of hypothalamic infundibular cells. These cells also act to pattern the adjacent neural tube.

Image 3. Knock-down of Sonic hedgehog in the floor plate by siRNA.

However, in contrast to floor plate cells, infundibular cells co-express Sonic hedgehog and members of the TGFbeta superfamily. The interaction of Sonic hedgehog and TGFbetas causes the induction of neurons with hypothalamic identity.

The key questions that we are currently addressing are:

• How infundibular cells come to be different from floor plate cells.
• The role that the infundibulum plays in hypothalamic patterning and neuronal differentiation.
• The mechanism by which Sonic hedgehog and TGFbetas co-operate in the hypothalamus.

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