Development, Vol 121, Issue 12 4339-4347, Copyright © 1995 by Company of Biologists

JOURNAL ARTICLES

Regulation of Hoxc-8 during mouse embryonic development: identification and characterization of critical elements involved in early neural tube expression

CS Shashikant, CJ Bieberich, HG Belting, JC Wang, MA Borbely and FH Ruddle
Department of Biology, Yale University, New Haven CT 06520, USA.

We have characterized cis-acting elements that direct the early phase of Hoxc-8 expression using reporter gene analysis in transgenic mice. By deletion we show that a 135 bp DNA fragment, located approximately 3 kb upstream of the coding region of Hoxc-8, is capable of directing posterior neural tube expression. This early neural tube (ENT) enhancer consists of four separate elements, designated A, B, C and D, whose nucleotide sequences are similar to binding sites of known transcription factors. Nucleotide substitutions suggest that element A is an essential component of the ENT enhancer. However element A by itself is incapable of directing neural tube expression. This element requires interactions at any two of the other three elements, B, C or D. Thus, the components of the ENT enhancer direct neural tube expression in an interdependent manner. We propose that Hoxc-8 is activated in the neural tube by combinatorial interactions among several proteins acting within a small region. Our transgenic analyses provide a means to identify transcription factors that regulate Hoxc-8 expression during embryogenesis.
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