BOTH 5'-ELEMENTS AND 3'-ELEMENTS TO THE MURINE HOXD4 GENE ESTABLISH ANTERIOR BORDERS OF EXPRESSION IN MESODERM AND NEURECTODERM

In this report, we show that a lacZ reporter spanning 12.5 kb of murin e Hoxd4 genomic DNA contains the major regulatory elements controlling Hoxd4 expression in the mouse embryo. Mutational analysis revealed mu ltiple regulatory regions both 5' and 3' to the coding region. These i nclude a 3' enhancer region required for expression in the central ner vous system (CNS) and setting the anterior border in the paraxial meso derm, and a 5' mesodermal enhancer that directs expression in paraxial and lateral plate mesoderm. A previously defined retinoic acid respon se element (RARE) is a component of the 5' mesodermal enhancer. Our re sults support a model in which retinoic acid receptors (RARs) and HOX proteins mediate the initiation and maintenance of Hoxd4 expression. ( C) 1997 Elsevier Science Ireland Ltd.