AP-2.2, a novel gene related to AP-2, is expressed in the forebrain, limbs and face during mouse embryogenesis

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/ULP/Collège de France, C.U. de Strasbourg.
Mechanisms of Development (Impact Factor: 2.24). 02/1996; 54(1):83-94. DOI: 10.1016/0925-4773(95)00463-7
Source: PubMed

ABSTRACT Using a differential subtractive hybridization cloning procedure we have recently identified the AP-2.2 gene as a novel early retinoic acid-induced gene in murine P19 embryonal carcinoma cells. We have also shown that the AP-2.2 protein, which is highly related to the AP-2 transcription factor, can activate transcription when bound to an AP-2 consensus binding site [Oulad-Abdelghani et al. (1995) Mol. Cell. Biol., submitted]. We report here the in situ hybridization pattern of expression of AP-2.2 transcripts during mouse embryogenesis. At 7.5 days post-coitum, AP-2.2 transcripts were detected in the boundary region between neural plate and surface ectoderm, as well as in extra-embryonic tissues. By 8.0-8.5 gestational days, AP-2.2 transcripts appeared to be expressed in premigratory and migrating neural crest cells. Over the following days, the AP-2.2 gene displayed region-restricted expression in the facial mesenchyme, especially around the embryonic mouth cavity and the nasal cavities, as well as in the surface ectoderm, nasal and oral epithelia. AP-2.2 RNA was also specifically expressed in the presumptive cortical region of the forebrain vesicles. AP-2.2 transcripts were restricted to the distal mitotic area (the 'progress zone') of the limb buds and of the genital bud. AP-2.2 expression also appeared to be specific for primordial germ cells in the genital ridges. Thus, the AP-2.2 gene is expressed in several embryonic areas whose development can be affected by retinoids, such as the forebrain, face and limb buds.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidermal morphogenesis begins with the commitment of the single-layered surface ectoderm to initiate a stratification program, a process that requires the expression of the transcription factor TAp63alpha. To determine the molecular mechanism by which TAp63alpha induces genes associated with the commitment to stratification, such as K14, we have used a combination of in vitro and in vivo approaches. Our initial gene expression profiling studies suggested that TAp63alpha could regulate one or more AP-2 genes, which have been implicated in development and maintenance of the epidermis. We now demonstrate that TAp63alpha directly induces AP-2gamma expression in embryonic epidermis, when commitment to stratification occurs. Furthermore, we show that, in the absence of AP-2gamma, TAp63alpha fails to induce K14 expression in vitro. Our data identify AP-2gamma as the first in vivo target gene of TAp63alpha, and provide novel insights into the molecular mechanisms associated with early events in epidermal morphogenesis.
    Developmental Biology 02/2006; 289(1):253-61. DOI:10.1016/j.ydbio.2005.10.041 · 3.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The transcription factor AP2 (TFAP2) has an important role in regulating gene expression in both epidermis and neural crest cells. In order to further characterize these functions we have used a hormone inducible TFAP2alpha fusion protein in a Xenopus animal cap assay to identify downstream targets of this factor. The most common pattern comprised genes predominantly expressed in the epidermis. A second group was expressed at high levels in the neural crest, but all of these were also expressed in the epidermis as well as in other tissues in which TFAP2alpha has not been detected, suggesting modular control involving both TFAP2-dependent and TFAP2-independent components. In addition, a few strongly induced genes did not overlap at all in expression pattern with that of TFAP2alpha in the early embryo, and were also activated precociously in the experimentally manipulated ectoderm, and thus likely represent inappropriate regulatory interactions. A final group was identified that were repressed by TFAP2alpha and were expressed in the neural plate. These results provide further support for the importance of TFAP2alpha in ectoderm development, and also highlight the molecular linkage between the epidermis and neural crest in the Xenopus embryo.
    Development Growth and Regeneration 09/2005; 47(6):403-13. DOI:10.1111/j.1440-169X.2005.00809.x · 2.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human birth defects involving the ventral body wall are common, yet little is known about the mechanism of body wall closure in mammals. The AP-2alpha transcription factor knock-out mouse provides an exceptional tool to understand this particular pathology, since it has one of the most severe ventral body wall closure defects, thoracoabdominoschisis. To gain insight into the complex morphological events responsible for body wall closure, we have studied this developmental process in AP-2alpha knock-out mice. Several tissues involved in normal ventral body wall closure are defective in the absence of AP-2alpha, including those associated with the primary body wall, the umbilical ring, and the mesoderm of the secondary body wall. These defects, coupled with the expression pattern of AP-2alpha, suggest that AP-2alpha is involved in multiple developmental mechanisms directing the morphogenesis of the ventral body wall, including cell migration, differentiation, and death. There is a failure of migration and fusion of the body folds at the umbilical ring, as well as in the formation and migration of the abdominal bands and ventral musculature. Furthermore, the mechanism of cell deposition at the umbilical ring is disturbed. Consequently, the mesodermal compartment of the body wall is underdeveloped. We also suggest that AP-2alpha is required for signaling from the surface ectoderm to the underlying mesoderm for proper development and closure of the ventral body wall. These findings provide a fundamental understanding of how AP-2alpha functions in the closure of the ventral body wall, as well as offer insight into related human birth defects.
    Developmental Biology 04/2004; 267(2):399-417. DOI:10.1016/j.ydbio.2003.11.021 · 3.64 Impact Factor