Identification of upstream regulators of Pax6 in sensory organ formation. (360G-Wellcome-081531_Z_06_Z)

Sense organs and sensory ganglia form the cranial sensory nervous system, crucial parts of which arise from placodes outside the CNS. We have recently found that all placode precursors share common properties and are initially specified as lens. When cultured in isolation, cells that normally never contribute to the lens undergo normal lens development. They rapidly begin to express Pax6 and other lens-specific genes culminating in the formation of crystallin+ lentoids. These findings provide a unique opportunity to study the molecular mechanisms that control Pax6 initiation in the future lens ectoderm. We have designed a differential screen using strict parameters to compare expression profiles of four different cell types. Taking advantage of a well defined biological system in which Pax6 expression is initiated within a short period, the screen considers timing of gene action as well as presence or absence of a certain set of markers genes. Using these stringent criteria we aim to identify only a few direct regulators of Pax6. Their function will then be assessed in gain- and loss-of-function approaches. The project will provide new insights into the specification of lens precursors and of progenitors that form the sensory nervous system.