Transcriptional control of forebrain regionalisation

Clemens Kiecker

Senior Lecturer

The formation of a broad array of neuronal cell types is one of the prerequisites for the establishment of functional brain architecture. We are interested in how this cellular diversity is generated in the forebrain—arguably the most complex subdivision of the vertebrate brain. Cell fate assignment in the developing CNS is governed by small groups of cells, called local organisers, that secrete signalling factors. These factors inform the cells in neighbouring tissues of their position and identity by initiating transcriptional changes and changing cellular behaviour, often in a dose-dependent fashion (Kiecker & Lumsden, 2012). A surprisingly small number of these secreted signals regulate the formation of hundreds of different cell types in the developing brain. Thus, additional mechanisms must be at work that modulate the response of different cells to the same signal—a phenomenon known as ‘differential competence’. Our work focuses on two secreted signals, SHH (Sonic hedgehog) and WNT, on the cellular responses that they elicit in different areas of the developing forebrain, and on the mechanism that regulate differential competence for these signals.