Variation and Transcriptional Control in Drosophila Segment Determination John Reinitz Stony Brook This talk will be concerned with two fundamental questions. The first is the determination of a morphogenetic field, and the second is the control of transcription in metazoan genes with large promoters. One of the central ideas in animal development is that of the determination of cell fates in a morphogenetic field. A second central idea, or perhaps observation, is that morphogenetic fields are capable of {\em regulation}, a classical term for the correction of errors. In the past, regulation was investigated by surgical perturbation of embryos. In the modern context regulation can also be studied in the context of genetic perturbations or of individual variations in gene expression in an isogenic population. We consider this problem in the early embryo of the fruit fly Drosophila, a well characterized system for molecular developmental genetics which can also be used as a naturally grown differential display system for reverse engineering networks of genes. This system is being used by ourselves and others to address fundamental questions about the reliability of developmental processes. In the Drosophila system which we study, determination of the morphogenetic field is implemented by means of differential regulation of transcription. The control of this process by groups of binding sites is as yet poorly understood. We present a new model of transcriptional control and show how it can be used to understand anomalous expression of even-skipped stripe 7 and to predict the results of site directed mutagenesis experiments.