Send to:

Choose Destination
See comment in PubMed Commons below
Dev Biol. 1998 Dec 1;204(1):197-209.

Distinct regulatory elements govern Fgf4 gene expression in the mouse blastocyst, myotomes, and developing limb.

Author information

  • 1Department of Microbiology, Skirball Institute and Kaplan Cancer Center, New York, New York, 10016, USA.


Embryonic development requires a complex program of events which are directed by a number of signaling molecules whose expression must be rigorously regulated. We previously showed that expression of Fgf4, which plays an important role in postimplantation development and growth and patterning of the limb, is regulated in EC cells by the synergistic interaction of Sox2 and Oct-3 with the Fgf4 EC cell-specific enhancer. To verify whether this mechanism was also operating in vivo, and to identify new elements controlling Fgf4 gene expression in distinct developmental stages, we have analyzed the expression of LacZ reporter plasmids containing different fragments of the Fgf4 gene in transgenic mouse embryos. Utilizing these transgenic constructs we have been able to recapitulate, for the most part, Fgf4 gene expression during embryonic development. We show here that most of the cis-acting regulatory elements determining Fgf4 embryonic expression are located in conserved regions within the 3' UTR of the gene. The EC cell-specific enhancer is required to drive gene expression in the ICM of the blastocyst, and its activity requires the Sox and Oct-proteins binding sites. We were also able to identify specific and distinct enhancer elements that govern postimplantation expression in the somitic myotomes and the limb bud AER. The myotome-specific elements contain binding sites for bHLH myogenic regulatory factors, which appear to be essential for myotome expression. Finally, we present evidence that the very restricted pattern of expression of Fgf4 transcripts in the AER results from the combined action of positive and negative regulatory elements located 3' of the Fgf4 coding sequences. Thus the Fgf4 gene relies on multiple and distinct regulatory elements to achieve stage- and tissue-specific embryonic expression.

Copyright 1998 Academic Press.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk