Establishing neuroblast-specific gene expression in the Drosophila CNS: huckebein is activated by Wingless and Hedgehog and repressed by Engrailed and Gooseberry

The Drosophila ventral neuroectoderm produces a stereotyped array of central nervous system precursors, called neuroblasts. Each neuroblast has a unique identity based on its position, pattern of gene expression and cell lineage. To understand how neuronal diversity is generated, we need to learn how neuroblast-specific gene expression is established, and how these genes control cell fate within neuroblast lineages. Here we address the first question: how is neuroblast-specific gene expression established? We focus on the huckebein gene, because it is expressed in a subset of neuroblasts and is required for aspects of neuronal and glial determination. We show that Huckebein is a nuclear protein first detected in small clusters of neuroectodermal cells and then in a subset of neuroblasts. The secreted Wingless and Hedgehog proteins activate huckebein expression in distinct but overlapping clusters of neuroectodermal cells and neuroblasts, whereas the nuclear Engrailed and Gooseberry proteins repress huckebein expression in specific regions of neuroectoderm or neuroblasts. Integration of these activation and repression inputs is required to establish the precise neuroectodermal pattern of huckebein, which is subsequently required for the development of specific neuroblast cell lineages.