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The zona limitans intrathalamica as an organiser of diencephalic development


The generation of the vertebrate brain relies on regionalisation of the neural plate through formation of boundaries. An important function of boundaries is to maintain the position of special groups of cells that are able to direct development of the neighbouring tissue. Such cell types form organisers and exert their action through secretion of long range signalling molecules. The formation of boundaries and their role in development of a forebrain region, the diencephalon, is still poorly understood. T he recent discovery of instructive activity of a diencephalic boundary, the zona limitans intrathalamica (ZLI), has raised new questions on its mechanism of action.

To understand the role of the ZLI in the development of the diencephalon we plan to first, identify the genetic programme induced by ZLI activity in the neighbouring tissue. Thereafter, we will select among the newly identified genes those with predicted value as lineage tracers and use their promoters to drive transgenic expression of an inducible Cre recombinase. Induction of Cre activity in a reporter mouse line will allow for the identification of neuronal progenitors induced by the ZLI and the analysis of their contribution to diencephalic architecture.

At the same time, some of the newly id entified genes will be tested for their function in diencephalic development by gain and loss of function experiments in chick and mouse. In addition to contributing to the understanding of the events that lead to the formation of the diencephalon, this re search will also complement my previous training in the transcriptional control of cell lineage commitment and development in the mouse, with important developmental neurobiology skills and the use of a new model system, the chick embryo. The resulting bro ad spectrum of research activity and intellectual expertise will strongly improve my carrier prospective for the future.

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