J. Beckers et al., Distinct regulatory elements direct Delta 1 expression in the nervous system and paraxial mesoderm of transgenic mice, MECH DEVEL, 95(1-2), 2000, pp. 23-34
The Delta1 gene encodes one of the Notch ligands in mice. Delta1 is express
ed during early embryogenesis in a complex and dynamic pattern in the parax
ial mesoderm and neuroectoderm, and is essential for normal somitogenesis a
nd neuronal differentiation. Molecular components thought to act in respons
e 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 g
ene 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 f
rom the primitive streak stage to early organogenesis, Using a minimal Delt
a1 promoter we also show that this upstream region contains distinct regula
tory modules that individually direct tissue-specific transgene expression
in subdomains of the endogenous expression pattern. It appears that express
ion in the paraxial mesoderm depends on the interaction of multiple positiv
e and negative regulatory elements. We also find that at least some regulat
ory 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 o
f Delta genes may be conserved. (C) 2000 Elsevier Science Ireland Ltd. All
rights reserved.