Dorsoventral patterning of the Drosophila embryonic central nervous system

The Drosophila embryonic central nervous system (CNS) develops from the ventrolateral region of the embryo, called the neuroectoderm. Neural stem cells arise from the neuroectoderm and acquire unique fates based on their position of formation. Previous work has identified four genes that pattern the dorsoventral axis of the neuroectoderm: the Drosophila EGF receptor (Egfr), ventral nerve cord defective (vnd), intermediate neuroblast defective (ind) and muscle segment homeobox (msh). The activity of these genes partitions the neuroectoderm into three parallel longitudinal columns (medial, intermediate, lateral) from which three columns of neural stem cells arise. My thesis focuses on understanding the genetic and molecular mechanisms that pattern the neuroectoderm along the dorsoventral axis.; My work demonstrates that the Sox-domain-containing gene Dichaete is a new factor that patterns the neuroectoderm along the dorsoventral axis. Dichaete is expressed in the medial and intermediate columns of the neuroectoderm and functions in parallel with vnd and ind, and downstream of Egfr signaling, to regulate neural stem cell formation and cell fate in these domains. To determine how vnd, ind and Dichaete regulate gene expression and cell fate at the molecular level. I defined a minimal CNS regulatory region of achaete, a putative direct downstream target of Vnd. Ind and Dichaete. I find that Dichaete and Ind interact physically and bind to juxtaposed binding sites within the ac regulatory region. These results suggest that Dichaete and Ind (and likely Vnd) act cooperatively to control CNS development through direct transcriptional regulation of target gene expression.; I have also combined loss of function analyses with ectopic activation of Egfr signaling to understand the genetic regulatory hierarchy that patterns the neuroectoderm. These studies allowed me to define the genetic criteria required to promote medial, intermediate and lateral column development and revealed that ind can repress vnd. Together these studies provide a more lucid picture of the genetic regulatory hierarchy that patterns the dorsoventral axis of the Drosophila CNS.