INTRODUCTION Extensive studies on the development of the Drosophila embryo have provided deep insight into the mechanisms governing embryonic pattern formation. These studies have focused primarily on the trunk region of the embryo and led to the discovery of an intricate cascade of hierarchical, cross- and autoregulatory gene interactions that progressively subdivide the embryo into increasingly smaller functional units (for review see e.g. Ingham, 1988; Pankratz and Jäckle, 1990). In contrast to the well understood segmentation of this central region, relatively little is known about the mechanisms involved in the patterning of the embryonic head. Recently, however, several genes have been identified that are involved in the segmentation of the topologically complex cephalic region (for review see Finkelstein and Perrimon, 1991; Cohen and Jürgens, 1991). Genetic analysis suggests that the mecha- nisms controlling head development may be different from the ones governing the segmentation of the trunk. To further our understanding of pattern formation in the head it is of utmost importance to unravel the genetic controls specifying the spatial expression of such head specific genes. In the Drosophila embryo the primary determination of cell fates along the anteroposterior and dorsoventral axes depends on the complex interaction of maternally expressed genes and zygotic effector genes (Nüsslein-Volhard et al., 1987; Manseau and Schüpbach, 1989). Three distinct groups of maternal coor- dinate genes are involved in the establishment of positions along the anteroposterior axis and one along the dorsoventral axis (see reviews by Nüsslein-Volhard, 1991; St. Johnston and Nüsslein-Volhard, 1992). The activity of these systems results in the spatially restricted transcriptional activation of zygotic genes that subdivide the embryo into different functional domains. Three maternal systems are required for proper development of the embryonic head: the anterior system deter- mining the head and thorax region, the terminal system, 3155 Development 120, 3155-3171 (1994) Printed in Great Britain © The Company of Biologists Limited 1994 In contrast to the segmentation of the embryonic trunk region which has been extensively studied, relatively little is known about the development and segmentation of the Drosophila head. Proper development of the cephalic region requires the informational input of three of the four maternal coordinate systems. Head-specific gene expression is set up in response to a complex interaction between the maternally provided gene products and zygot- ically expressed genes. Several zygotic genes involved in head development have recently been characterized. A genetic analysis suggests that the segmentation of the head may use a mechanism different from the one acting in the trunk. The two genes of the sloppy paired locus (slp1 and slp2) are also expressed in the embryonic head. slp1 plays a predominant role in head formation while slp2 is largely dispensible. A detailed analysis of the slp head phenotype suggests that slp is important for the development of the mandibular segment as well as two adjacent pregnathal segments (antennal and ocular). Our analysis of regulatory interactions of slp with maternal and zygotic genes suggests that it behaves like a gap gene. Thus, phenotype and regu- lation of slp support the view that slp acts as a head-specific gap gene in addition to its function as a pair-rule and segment polarity gene in the trunk. We show that all three maternal systems active in the cephalic region are required for proper slp expression and that the different systems cooperate in the patterning of the head. The terminal and anterior patterning system appear to be closely linked. This cooperation is likely to involve a direct interaction between the bcd morphogen and the terminal system. Low levels of terminal system activity seem to potentiate bcd as an activator of slp, whereas high levels down-regulate bcd rendering it inactive. Our analysis suggests that dorsal, the morphogen of the dorsoventral system, and the head- specific gap gene empty spiracles act as repressor and co- repressor in the regulation of slp. We discuss how posi- tional information established independently along two axes can act in concert to control gene regulation in two dimensions. Key words: Drosophila, head development, maternal coordinate systems, sloppy paired locus, transcriptional regulation SUMMARY Three maternal coordinate systems cooperate in the patterning of the Drosophila head Ueli Grossniklaus*, Kenneth M. Cadigan † and Walter J. Gehring Department of Cell Biology, Biozentrum of the University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland *Present address: Cold Spring Harbor Laboratory, 1, Bungtown Road, P.O. Box 100, Cold Spring Harbor, NY 11724, USA † Present address: Howard Hughes Medical Institue and Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford CA 94305-5428, USA