Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 28, Issue 1, Pages 315-325Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01168-07
Keywords
-
Categories
Funding
- NIDCR NIH HHS [R01 DE12728, R01 DE012728] Funding Source: Medline
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE012728] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Tcfap2a, the gene encoding the mouse AP-2 alpha transcription factor, is required for normal development of multiple structures during embryogenesis, including the face and limbs. Using comparative sequence analysis and transgenic-mouse experiments we have identified an intronic enhancer within this gene that directs expression to the face and limb mesenchyme. There are two conserved sequence blocks within this intron, and the larger of these directs tissue-specific activity and is found in all vertebrate Tcfap2a genes analyzed. To assess the role of the enhancer in regulating endogenous mouse Tcfap2a expression, we have deleted this cis-regulatory sequence from the genome. Loss of this element severely impairs Tcfap2a expression in the limb bud mesenchyme but generates only a modest reduction in the facial mesenchyme. The reduction in Tcfap2a transcription is accompanied by altered patterning of the forelimb, resulting in postaxial polydactyly. These results indicate that the major role for this enhancer resides within the limb bud, and it serves to maintain a level of Tcfap2a expression that limits the size of the hand plate and the associated number of digit primordia. The potential role of this cis-acting sequence in modeling the size and shape of the face and limbs during evolution is discussed.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available