Dolle P. 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: 2.44). 02/1996; 54(1):83-94. DOI: 10.1016/0925-4773(95)00463-7
Source: PubMed


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
    • "Moreover, Wnt3a and Fgf15 defines the entire alar plate of p2 (thalamus and epithalamus), whereas Gbx2 and Sox14 are expressed in the thalamic domain but not the epithalamus (Figures 2C,G; Bulfone et al., 1993; Martinez-de-la-Torre et al., 2002; Gimeno et al., 2003). The caudal limit of Gbx2 expression domain (Figures 2A,C,G), together with the AP-2 (Chazaud et al., 1996) and Ebf-1/2/3 (Garel et al., 1997) gene expressions in p1 allows to establish the molecular boundary between p1 and p2. Actually, in zebrafish this boundary requires Lhx2/9 expression and Wnt signaling to develop normally (Peukert et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The anatomic complexity of the diencephalon depends on precise molecular and cellular regulative mechanisms orchestrated by regional morphogenetic organizers at the neural tube stage. In the diencephalon, like in other neural tube regions, dorsal and ventral signals codify positional information to specify ventro-dorsal regionalization. Retinoic acid, Fgf8, BMPs, and Wnts signals are the molecular factors acting upon the diencephalic epithelium to specify dorsal structures, while Shh is the main ventralizing signal. A central diencephalic organizer, the zona limitans intrathalamica (ZLI), appears after neurulation in the central diencephalic alar plate, establishing additional antero-posterior positional information inside diencephalic alar plate. Based on Shh expression, the ZLI acts as a morphogenetic center, which cooperates with other signals in thalamic specification and pattering in the alar plate of diencephalon. Indeed, Shh is expressed first in the basal plate extending dorsally through the ZLI epithelium as the development proceeds. Despite the importance of ZLI in diencephalic morphogenesis the mechanisms that regulate its development remain incompletely understood. Actually, controversial interpretations in different experimental models have been proposed. That is, experimental results have suggested that (i) the juxtaposition of the molecularly heterogeneous neuroepithelial areas, (ii) cell reorganization in the epithelium, and/or (iii) planar and vertical inductions in the neural epithelium, are required for ZLI specification and development. We will review some experimental data to approach the study of the molecular regulation of diencephalic regionalization, with special interest in the cellular mechanisms underlying planar inductions.
    Full-text · Article · May 2012 · Frontiers in Neuroscience
  • Source
    • "In mammals, five Ap-2 genes (Tcfap2a to e) exist, which encode for the Ap-2α to ε proteins. Ap-2α, Ap-2β and Ap-2γ show partially overlapping expression patterns in neural crest cells, the central and peripheral nervous system, the facial mesenchyme, the limbs, various epithelia of the developing embryo, and the extraembryonic trophectoderm [2], [3], [4]. In contrast, the more recently characterized Ap-2 transcription factors, Ap-2δ and Ap-2ε, show a more restricted expression pattern and are almost exclusively expressed in the central nervous system. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ap-2 transcription factors comprise a family of 5 closely related sequence-specific DNA binding proteins that play pivotal and non-redundant roles in embryonic organogenesis. To investigate the function of Ap-2δ, wδe analyzed its expression during embryogenesis and generated Ap-2δ-deficient mice. In line with the specific expression pattern of Ap-2δ in the mesencephalic tectum and the dorsal midbrain, Ap-2δ-deficient mice failed to maintain the colliculus inferior, a derivative of the dorsal midbrain, as a consequence of increased apoptotic cell death. To identify specific Ap-2δ target genes in cells of the developing dorsal midbrain, we performed whole genome analysis of cDNA expression levels. This approach identified a set of 12 putative target genes being expressed in the developing midbrain, including the transcription factors Pitx2, Mef2c, Bhlhb4 and Pou4f3. Using chromatin immunoprecipitation (CHIP) we showed that some of these genes are direct targets of Ap-2δ. Consistently, we demonstrate that Ap-2δ occupies and activates the Pou4f3 and Bhlhb4 promoters. In addition, known Pou4f3 target genes were downregulated in the posterior midbrain of Ap-2δ-deficient mice. Despite the absence of a central part of the auditory pathway, the presence of neuronal responses to sounds in the neocortex of Ap-2δ-deficient mice indicates that auditory information from the brainstem still reaches the neocortex. In summary, our data define Ap-2δ as an important transcription factor, specifying gene expression patterns required for the development of the posterior midbrain.
    Full-text · Article · Aug 2011 · PLoS ONE
  • Source
    • "During murine development Tcfap2c expression is restricted spatiotemporal to facial and limb mesenchyme, extraembryonic tissue, primordial germ cells, peripheral nervous system, neural-crest cells, dorsal telencephalon and various epithelia of the developing embryo [12]. In adults, its expression is limited to the developing breast, where loss of Tcfap2c blocks branching morphogenesis of the mammary gland before puberty [13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The transcription factor Tcfap2c has been demonstrated to be essential for various processes during mammalian development. It has been found to be upregulated in various undifferentiated tumors and is implicated with poor prognosis. Tcfap2c is reported to impinge on cellular proliferation, differentiation and apoptosis. However, the physiological consequences of Tcfap2c-expression remain largely unknown. Therefore we established a gain of function model to analyze the role of Tcfap2c in development and disease. Induction of the transgene led to robust expression in all tissues (except brain and testis) and lead to rapid mortality within 3-7 days. In the liver cellular proliferation and apoptosis was detected. Accumulation of microvesicular lipid droplets and breakdown of major hepatic metabolism pathways resulted in steatosis. Serum analysis showed a dramatic increase of enzymes indicative for hepatic failure. After induction of Tcfap2c we identified a set of 447 common genes, which are deregulated in both liver and primary hepatocyte culture. Further analysis showed a prominent repression of the cytochrome p450 system, PPARA, Lipin1 and Lipin2. These data indicate that in the liver Tcfap2c represses pathways, which are responsible for fatty acid metabolism. In the intestine, Tcfap2c expression resulted in expansion of Sox9 positive and proliferative active epithelial progenitor cells resulting in dysplastic growth of mucosal crypt cells and loss of differentiated mucosa. The transgenic mice show that ectopic expression of Tcfap2c is not tolerated. Due to the phenotype observed, iTcfap2c-mice represent a model system to study liver failure. In intestine, Tcfap2c induced cellular hyperplasia and suppressed terminal differentiation indicating that Tcfap2c serves as a repressor of differentiation and inducer of proliferation. This might be achieved by the Tcfap2c mediated activation of Sox9 known to be expressed in intestinal and hepatic stem/progenitor cell populations.
    Full-text · Article · Jul 2011 · PLoS ONE
Show more