Distinct regulatory elements direct delta1 expression in the nervous system and paraxial mesoderm of transgenic mice

The Delta1 gene encodes one of the Notch ligands in mice. Delta1 is expressed during early embryogenesis in a complex and dynamic pattern in the paraxial mesoderm and neuroectoderm, and is essential for normal somitogenesis and neuronal differentiation. Molecular components thought to act in response to ligand binding and Notch activation have been identified in different species. In contrast, little is known about the transcriptional regulation of Notch receptors and their ligands. As a first step to identify upstream factors regulating Delta1 expression in different tissues, we searched for cis-regulatory regions in the Delta1 promoter able to direct heterologous gene expression in a tissue specific manner in transgenic mice. Our results show that a 4.3 kb genomic DNA fragment of the Delta1 gene is sufficient in a lacZ reporter transgene to reproduce most aspects of Delta1 expression from the primitive streak stage to early organogenesis. Using a minimal Delta1 promoter we also show that this upstream region contains distinct regulatory modules that individually direct tissue-specific transgene expression in subdomains of the endogenous expression pattern. It appears that expression in the paraxial mesoderm depends on the interaction of multiple positive and negative regulatory elements. We also find that at least some regulatory sequences required for transgene expression in subdomains of the neural tube have been maintained during the evolution of mammals and teleost fish, suggesting that part of the regulatory network that controls expression of Delta genes may be conserved.