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Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins
Author(s) -
Donner Amy L.,
Williams Trevor
Publication year - 2006
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20722
Subject(s) - biology , enhancer , genetics , neural crest , limb development , transcription factor , gene , transgene , regulatory sequence , conserved sequence , limb bud , microbiology and biotechnology , peptide sequence
The AP‐2 transcription factor family is linked with development of the head and limbs in both vertebrate and invertebrate species. Recent evidence has also implicated this gene family in the evolution of the neural crest in chordates, a critical step that allowed the development and elaboration of the vertebrate craniofacial skeleton. In mice, the inappropriate embryonic expression of one particular AP‐2 gene, Tcfap2a , encoding AP‐2α, results in multiple developmental abnormalities, including craniofacial and limb defects. Thus, Tcfap2a provides a valuable genetic resource to analyze the regulatory hierarchy responsible for the evolution and development of the face and limbs. Previous studies have identified a 2‐kilobase intronic region of both the mouse and human AP‐2α locus that directs expression of a linked LacZ transgene to the facial processes and the distal mesenchyme of the limb bud in transgenic mice. Further analysis identified two highly conserved regions of ∼200–400 bp within this tissue‐specific enhancer. We have now initiated a transgenic and biochemical analysis of the most important of these highly conserved regions. Our analysis indicates that although the sequences regulating face and limb expression have been integrated into a single enhancer, different cis ‐acting sequences ultimately control these two expression domains. Moreover, these studies demonstrate that a conserved STAT binding site provides a major contribution to the expression of Tcfap2a in the facial prominences. Developmental Dynamics 235:1358–1370, 2006. © 2006 Wiley‐Liss, Inc.