- Research article
- Open Access
Novel gene expression patterns along the proximo-distal axis of the mouse embryo before gastrulation
© Frankenberg et al; licensee BioMed Central Ltd. 2007
- Received: 02 November 2006
- Accepted: 15 February 2007
- Published: 15 February 2007
To date, the earliest stage at which the orientation of the anterior-posterior axis in the mouse embryo is distinguishable by asymmetric gene expression is shortly after E5.5. At E5.5, prospective anterior markers are expressed at the distal tip of the embryo, whereas prospective posterior markers are expressed more proximally, close to the boundary with the extraembryonic region.
To contribute to elucidating the mechanisms underlying the events involved in early patterning of the mouse embryo, we have carried out a microarray screen to identify novel genes that are differentially expressed between the distal and proximal parts of the E5.5 embryo. Secondary screening of resulting candidates by in situ hybridisation at E5.5 and E6.5 revealed novel expression patterns for known and previously uncharacterised genes, including Peg10, Ctsz1, Cubilin, Jarid1b, Ndrg1, Sfmbt2, Gjb5, Talia and Plet1. The previously undescribed gene Talia and recently identified Plet1 are expressed specifically in the distal-most part of the extraembryonic ectoderm, adjacent to the epiblast, and are therefore potential candidates for regulating early patterning events. Talia and the previously described gene XE7 define a gene family highly conserved among metazoans and with a predicted protein structure suggestive of a post-transcriptional regulative function, whilst Plet1 appears to be mammal-specific and of unknown function.
Our approach has allowed us to compare expression between dissected parts of the egg cylinder and has identified multiple genes with novel expression patterns at this developmental stage. These genes are potential candidates for regulating tissue interactions following implantation.
- Imprint Gene
- Primitive Streak
- Visceral Endoderm
- Ectoplacental Cone
- Extraembryonic Ectoderm
At 5.5 days of development (E5.5) the mouse egg cylinder appears radially symmetrical about its proximo-distal axis with respect to known molecular markers and to the arrangement of its three principle tissue layers – epiblast, extra-embryonic ectoderm and visceral endoderm. However, shortly after E5.5 the first molecular asymmetries that determine the anterior-posterior axis begin to emerge. These involve movement of a subset of visceral endoderm cells, anterior visceral endoderm (AVE), located at the distal tip of the egg cylinder towards the future anterior side [1–5]. Subsequent to this, molecular markers with a previously radial distribution near the embryonic-extra-embryonic boundary become restricted to the future posterior side at the site of the emerging primitive streak . In this way the proximo-distal signaling anticipates the anterior-posterior patterning [6, 7]. Patterning thus occurs through a combination of tissue interactions and cell movements [reviewed ].
The stages of mouse development between implantation and the gastrulating egg cylinder have been relatively little studied. This is due partly to the relative inaccessibility of embryos within the uterine deciduae during this time, and partly to their relatively poor development in culture compared with preimplantation and gastrula stages. More recently, much attention has been focused on the events preceding gastrulation and their relation to earlier preimplantation development, providing an incentive to identify novel genes with restricted expression patterns during these stages.
Several recent microarray screens have focused on stage-specific expression in pre-implantation embryos [9–11], whilst other screening strategies have targeted specific tissues of post-implantation embryos [12–15]. In an effort to identify new genes that are differentially expressed along the proximo-distal axis and may have roles in early pre-gastrula patterning events, we employed microarray analysis to compare gene expression between proximal and distal halves of the E5.5 egg cylinder. The proximal half includes extraembryonic ectoderm and the proximal portion of the visceral endoderm, while, the distal half includes the epiblast and the distal portion of the visceral endoderm. After secondary screening by in situ hybridisation, we identified both known and novel genes with previously unreported differential expression in the early mouse egg cylinder.
Summary of genes with restricted expression patterns
NIA clone ID
Tissue with specific expression
epiblast + ectoplacental cone
extraembryonic ectoderm + node
extraembryonic ectoderm + node
Expression patterns fell into several broad categories. Peg10, Ctsz and Cubilin were expressed in the visceral endoderm mainly within the proximal or "extraembryonic" part of the egg cylinder. The expression of Cubilin also extended into the distal portion of the egg cylinder in the form of two lateral "wings" overlying the epiblast. Tissue sectioning showed that this expression corresponds to the distal extent of cuboidal visceral endoderm cells (Fig. 3a, b).
Two genes, and Gjb5 and Sfmbt2, were expressed throughout the extraembryonic ectoderm. In sectioned embryos, Sfmbt2 expression appeared uniform within the chorionic ectoderm and also within the ectoplacental cone until at least E7.5 (Fig. 3c, d). Sfmbt2 expression was also detected in all adult tissues tested but was substantially stronger in brain, lung and spleen compared with heart, kidney and liver (Fig. 4).
Ndrg1 was expressed uniformly throughout the extraembryonic ectoderm but more strongly within the labyrinth of the ectoplacental cone in all stages examined (Fig. 2, Fig. 3). At E7.5 and E8.0 (Fig. 2, 3f), expression was also present in the node, while becoming weaker within the chorionic ectoderm. No specific expression in other embryonic tissues was detected later at either E8.5 or E9.5 (not shown).
Plet1 was also specifically expressed in the extraembryonic ectoderm, but restricted to its distal-most part as early as E5.5 as well as a separate domain of much stronger expression within the ectoplacental cone. The distally-restricted expression persisted, but becoming weaker and restricted to the peripheral chorion, until at least E8.5 (Fig. 2, 3g–h). Expression was also detected within the ventral layer of the node (Fig. 3i).
A previously undescribed gene corresponding to clone H3001D07-3 was also uniformly expressed in the extraembryonic ectoderm at E5.5, and by E6.5 was also restricted to its more distal part, adjacent to the epiblast. Although levels appeared lower at later stages, expression appeared to be strongest around the perimeter of the distal part of the chorionic ectoderm at E7.5 (Fig. 3j). Expression was detected ubiquitously in all adult tissues examined by RT-PCR (Fig. 4).
A BLAST search of genomic databases identified the gene as mapping to region XA2 of the murine X-chromosome. A human orthologue was also identified in the syntenic region Xq24 of the human X-chromosome and in the marsupial Monodelphis domestica by sequence database searches, indicating that the gene is conserved in mammals. The 5'-most part of the predicted transcript also showed homology to another previously described human gene, XE7, which maps to Xp22.3 of the X-chromosome and was originally identified as a pseudoautosomal gene that escapes X inactivation [23, 24] and encodes a cell surface glycoprotein expressed in trophoblast and lymphocytes . The murine gene represented by clone H3001D07-3 we thus named Talia (a Polish word for "waistline") to reflect its belt-like expression pattern in the distal part of the extraembryonic ectoderm.
Sequence analysis of Talia and XE7
Talia/TALIA appears to be specific to mammals, being more divergent than XE7 from homologues in other metazoans, and apparently represents the only conserved evolutionary duplication of the ancestral gene detectable in genomic databases. Functional orthologues of Talia in pig and rat are supported by EST evidence, however human TALIA is apparently not expressed, as no corresponding ESTs were identified in existing databases. Furthermore, the human genomic sequence (LOC139516) contains two premature in-frame stop codons (corresponding to positions 234 and 348 in Fig. 6), suggesting that it is non-functional. Conversely, many more ESTs for human XE7 appeared to be present in databases compared with those for murine Xe7, raising the possibility that mammalian XE7 and TALIA have overlapping roles and may variously substitute for one another in different species.
This study identified a number of genes with previously unreported differential expression in the early postimplantation mouse embryo. Several represent new candidates for genes involved in tissue interactions controlling early events upon implantation. Three genes identified in the screen – Peg10, Ctsz and Cubilin – showed specific expression in the visceral endoderm of the egg cylinder. The human orthologue of Peg10 was originally identified as a paternally expressed imprinted gene with homologies in two open reading frames to gag and pol proteins of some vertebrate retrotransposons . It forms part of a novel imprinted gene cluster on human chromosome 7  and mouse chromosome 6  and has been shown to have oncogenic activity in hepatoma cells, suggesting a role in cell proliferation . Cathepsin Z, encoded by Ctsz, is a member of the C1 family of cysteine proteases of unknown function. The gene lies proximal to a cluster of imprinted genes but is not itself imprinted . Previously, Ctsz was reported as ubiquitously expressed in adult tissues . This study, however, shows that Ctsz has tissue-specific expression at least in the early post-implantation embryo.
Cubilin encodes a multiligand endocytic receptor involved in uptake of low density lipoproteins and is present in absorptive epithelia of the ileum, kidney and visceral yolk sac [reviewed in: [35, 36]]. Its lateral endodermal expression overlying the epiblast at both E6.5 and E7.5 is of interest as it may reflect the movements of this tissue during early gastrulation (Thomas et al, 1998; Perea-Gomez et al, 2001). While no antero-posterior asymmetry was evident in the expression of Cubilin alone, it would be interesting to investigate the degree to which it overlaps with AVE markers such as Lefty1 [37, 38], Cer1  and particularly Dkk1, which is expressed in the more proximal part of the embryonic VE from E5.25 and of the later AVE .
Jarid1b showed expression in epiblast and the outer part of the ectoplacental cone at E5.5, however by E6.5 epiblast expression was weak or undetectable. Jarid1b encodes a nuclear protein that was originally identified in human breast cancer cell lines . In normal adult tissues of human and mouse, expression is largely restricted to testis and ovary [41, 42]. In E12.5-15.5 mouse embryos, expression occurs in a spatially restricted pattern that overlaps with those of Bf-1 and Pax-9 [42, 43], with which PLU-1 has been shown to interact .
Three genes – Ndrg1, Sfmbt2 and Gjb5 – identified in the screen showed specific expression throughout the extraembryonic ectoderm at both E5.5 and E6.5. Ndrg1 was originally identified by its upregulation in N-myc deficient mice . While its precise function remains obscure, it has been reported to be involved in cell growth and differentiation [45–48]. Sfmbt2 is related to the Drosophila polycomb group of transcriptional repressors, which regulate homeotic and other genes [49–51]. The closely related murine gene Sfmbt1 (= Sfmbt) was shown to be highly expressed in adult testis, with a much lower expression in other adult and late embryonic tissues . Sfmbt2 has not been characterised, however database searches of matching ESTs indicate expression in testis and germ cells, suggesting that Sfmbt1 and Sfmbt2 may have related roles.Gjb5, which showed very strong specific expression in the extra-embryonic ectoderm, encodes one of a large family of gap junction proteins. A number of other gap junction proteins also show spatially restricted expression during early post-implantation development, indicative of a role in establishing communication compartments [53, 54], whilst Gjb5 expression has previously been shown in preimplantation embryos . While the roles of gap junctions during early development remain unclear, it is possible they may help to facilitate the transduction of signalling molecules within tissues.
Two genes – Plet1 and Talia – showed localised expression in the extraembryonic ectoderm that may suggest a role in the interactions between epiblast and extraembryonic ectoderm. Signals from this region of the egg cylinder are believed to regulate proximo-distal patterning of the epiblast via such factors as Nodal, Cripto and Otx2 [5, 17, 56–62]. Proximo-distal signaling contributes to anterior-posterior patterning via asymmetric cell movements that position the AVE opposite the site of primitive streak formation. The specific identity of extraembryonic ectoderm adjacent to the epiblast is thought to be regulated by Fgf4 signaling via activation of the Erk pathway (reviewed ). Thus it is likely that expression of Plet1 and Talia is regulated downstream of this signaling, and may have roles in specifying this identity. In particular, the restricted expression of Plet1 from E5.5 appears to be earlier than has been reported for other genes such as Eomes  and Bmp4 , suggesting that Plet1 expression may be directly regulated by this pathway. Recently identified by its trophoblast-specific expression at later stages of mouse, pig and human [66, 67], no functional motifs are evident to suggest a role for the protein.
By contrast, we have shown from its predicted tertiary structure that Talia is likely to function as a post-transcriptional regulator due to its similarities with HuD, an RNA-binding protein shown to have a role in specifying neural cell identity . Interestingly the role of Talia is possibly substituted by a homologue, XE7, in humans. The high conservation of orthologues of Talia/XE7 amongst metazoans further supports an essential role in development.
This study demonstrated for the first time the application of a microarray strategy for identifying genes that are differentially expressed between dissected parts of the early post-implantation mouse embryo. It successfully identified several genes, both known and previously uncharacterised, with novel expression patterns in the early mouse post-implantation embryo. Some of these, such as Talia and Plet1, will be of particular interest for further analysis, particularly with respect to possible roles in specifying the identity of extraembryonic ectoderm adjacent to the epiblast or in signaling to the proximal epiblast.
Fifty E5.5 embryos from F1 (C57/BL6 × CBA) females crossed with F1 males were collected into M2 medium. After removal of Reichert's membrane, embryos were cut at the embryonic-extraembryonic boundary into proximal and distal halves, using a finely drawn glass needle, respectively pooled, frozen on dry ice and stored at -80C until RNA extraction.
Preparation of labelled target cDNA
Total RNA was extracted using an RNeasy Mini Kit (Qiagen) according to the manufacturer's instructions. Target cDNA synthesis and single primer amplification (SPA) followed by labelling with Cy5- or Cy3-dCTP were performed as previously described . Labelled target cDNA was hybridised to an array of plates 3001–3048 of the NIA 15 K mouse cDNA set  spotted in duplicate (4608 ESTs, 9216 spots) on CMT-GAPS-coated slides (Corning) and analysed as previously described . Candidate genes were selected on the basis of both ratio and absolute difference in hybridisation level of each of the target cDNAs. Clone names used below can be identified via the NIA/NIH Mouse Genomics website .
Whole mount in situhybridisation
E5.5 and E6.5 embryos were collected as above and, after removal of Reichert's membrane, fixed in 4% paraformaldehyde in phosphate buffered saline overnight at 4°C. DNA templates were prepared by PCR from plasmid DNA using T3, SP6 and T7 promoter-specific primers. Plasmid templates for each probe were either transcribed directly from NIA clones (corresponding to those used in the array) or were cloned by RT-PCR from E6.5 embryo mRNA into the EcoRI and SalI sites of pBluescript II KS(+). Respective forward and reverse primers for the latter were: Jarid1b, 5'-GGAATTCGGGTTGCTTGCTTCTGCTTCTTC and 5'-GCGTCGACATCAGGGGAAACTGGTATCGGC; Gjb5, 5'-GGAATTCCTACCTCTTCCACGCATTCTATCC and 5'-GCGTCGACAGGCATTTGCTCATCGGTGC; Sfmbt2, 5'-GGAATTCGTCTCTGGGGACATCTACTGCTTG and 5'-GCGTCGACTGCTCTGCCTCGGTTCTGTG; Ndrg1, 5'-GGAATTCGAGAGAGAGAGGCAGGAAAGTTGG and 5'-GCGTCGACTACAAACCCAGTCAGCAGGAGG; Cubilin, 5'-GGAATTCAACCTTGCCCGTGTTCTATTCC and 5'-GCGTCGACTGAAGACCCGATTTGATGAAGC; Talia (exon 7), 5'-GGAATTCATCCTGGCACATCAATAATGGC and 5'-GCGTCGACAAGTAACCCCACAGACTGACATCC; Talia (exons 3–4), CATTTTCTGCATAAGGTGGTGTGAGGAC and GCCTGATAGCATCGCTTCTCTGCC;Plet1, 5'-GGAATTCCTGAAAGCAGTGAAGGAGGACG and 5'-GCGTCGACCACGCAGGATGGATGGACTAAG.
Digoxygenin-labelled antisense RNA probes were prepared using an Ambion MegaScript transcription kit (SP6, T3 or T7) according to the manufacturer's instructions. In situ hybridisation was performed as described by Wilkinson and Nieto .
Genomic structure was analysed using the Genomatix web-based sequence analysis software. ESTs were searched using BLAST and sequence alignments performed using MacVector. Protein secondary structure prediction and similarity searches were performed using the 3D-PSSM web-based software [73, 74].
Analysis of expression by RT-PCR
Total RNA was extracted from adult female mouse tissues and pooled E7.5 egg cylinders using the RNeasy Mini Kit (QIAGEN) according to the manufacturers instructions. Oligo-dT(20)-primed first strand cDNA was prepared from 0.5 μg of total RNA in a 10-μl reaction volume using SuperScript III (Invitrogen) at 50°C for 1 hour according to the manufacturer's instructions. 0.5 μL of template was then used for each 15-μL PCR reaction mixture containing 0.05 Units/μL GoTaq polymerase (Promega), 1× supplied PCR buffer, 0.25 mM dNTPs and 0.5 μM each of forward and reverse gene-specific primers. 35 cycles of PCR were performed comprising 15 seconds denaturation (94°C), 15 seconds annealing (55°C) and 30 seconds extension (72°C). 8 μL of each PCR product was separated by electrophoresis in a 1.5% agarose gel containing ethidium bromide.
This work was funded by Human Frontiers Scientific Programme and Wellcome Trust grants to MZG. MZG also thanks the Wellcome Trust for her Senior Research Fellowship. The microarrays used in this study were made available free of charge by the HGMP Resource Centre, Hinxton, UK. We thank Dr Mark DePristo for assistance in protein structure analysis and Dr Claire Chazaud for support during the latter part of the study.
- Thomas PQ, Brown A, Beddington RS: Hex: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors. Development. 1998, 125 (1): 85-94.PubMedGoogle Scholar
- Weber RJ, Pedersen RA, Wianny F, Evans MJ, Zernicka-Goetz M: Polarity of the mouse embryo is anticipated before implantation. Development. 1999, 126 (24): 5591-5598.PubMedGoogle Scholar
- Rivera-Perez JA, Mager J, Magnuson T: Dynamic morphogenetic events characterize the mouse visceral endoderm. Dev Biol. 2003, 261 (2): 470-487. 10.1016/S0012-1606(03)00302-6.View ArticlePubMedGoogle Scholar
- Srinivas S, Rodriguez T, Clements M, Smith JC, Beddington RS: Active cell migration drives the unilateral movements of the anterior visceral endoderm. Development. 2004, 131 (5): 1157-1164. 10.1242/dev.01005.View ArticlePubMedGoogle Scholar
- Yamamoto M, Saijoh Y, Perea-Gomez A, Shawlot W, Behringer RR, Ang SL, Hamada H, Meno C: Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo. Nature. 2004, 428 (6981): 387-392. 10.1038/nature02418.View ArticlePubMedGoogle Scholar
- Beddington RS, Robertson EJ: Axis development and early asymmetry in mammals. Cell. 1999, 96 (2): 195-209. 10.1016/S0092-8674(00)80560-7.View ArticlePubMedGoogle Scholar
- Liu P, Wakamiya M, Shea MJ, Albrecht U, Behringer RR, Bradley A: Requirement for Wnt3 in vertebrate axis formation. Nat Genet. 1999, 22 (4): 361-365. 10.1038/11932.View ArticlePubMedGoogle Scholar
- Zernicka-Goetz M: Patterning of the embryo: the first spatial decisions in the life of a mouse. Development. 2002, 129 (4): 815-829.PubMedGoogle Scholar
- Wang QT, Piotrowska K, Ciemerych MA, Milenkovic L, Scott MP, Davis RW, Zernicka-Goetz M: A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo. Dev Cell. 2004, 6 (1): 133-144. 10.1016/S1534-5807(03)00404-0.View ArticlePubMedGoogle Scholar
- Sharov AA, Piao Y, Matoba R, Dudekula DB, Qian Y, VanBuren V, Falco G, Martin PR, Stagg CA, Bassey UC, Wang Y, Carter MG, Hamatani T, Aiba K, Akutsu H, Sharova L, Tanaka TS, Kimber WL, Yoshikawa T, Jaradat SA, Pantano S, Nagaraja R, Boheler KR, Taub D, Hodes RJ, Longo DL, Schlessinger D, Keller J, Klotz E, Kelsoe G, Umezawa A, Vescovi AL, Rossant J, Kunath T, Hogan BL, Curci A, D'Urso M, Kelso J, Hide W, Ko MS: Transcriptome analysis of mouse stem cells and early embryos. PLoS Biol. 2003, 1 (3): E74-10.1371/journal.pbio.0000074.PubMed CentralView ArticlePubMedGoogle Scholar
- Hamatani T, Carter MG, Sharov AA, Ko MS: Dynamics of global gene expression changes during mouse preimplantation development. Dev Cell. 2004, 6 (1): 117-131. 10.1016/S1534-5807(03)00373-3.View ArticlePubMedGoogle Scholar
- Sousa-Nunes R, Rana AA, Kettleborough R, Brickman JM, Clements M, Forrest A, Grimmond S, Avner P, Smith JC, Dunwoodie SL, Beddington RS: Characterizing embryonic gene expression patterns in the mouse using nonredundant sequence-based selection. Genome Res. 2003, 13 (12): 2609-2620. 10.1101/gr.1362303.PubMed CentralView ArticlePubMedGoogle Scholar
- Shimono A, Behringer RR: Differential screens with subtracted PCR-generated cDNA libraries from subregions of single mouse embryos. Methods Mol Biol. 2000, 136: 333-344.PubMedGoogle Scholar
- Ko MS, Threat TA, Wang X, Horton JH, Cui Y, Pryor E, Paris J, Wells-Smith J, Kitchen JR, Rowe LB, Eppig J, Satoh T, Brant L, Fujiwara H, Yotsumoto S, Nakashima H: Genome-wide mapping of unselected transcripts from extraembryonic tissue of 7.5-day mouse embryos reveals enrichment in the t-complex and under-representation on the X chromosome. Hum Mol Genet. 1998, 7 (12): 1967-1978. 10.1093/hmg/7.12.1967.View ArticlePubMedGoogle Scholar
- Harrison SM, Dunwoodie SL, Arkell RM, Lehrach H, Beddington RS: Isolation of novel tissue-specific genes from cDNA libraries representing the individual tissue constituents of the gastrulating mouse embryo. Development. 1995, 121 (8): 2479-2489.PubMedGoogle Scholar
- Simeone A, Acampora D, Mallamaci A, Stornaiuolo A, D'Apice MR, Nigro V, Boncinelli E: A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. Embo J. 1993, 12 (7): 2735-2747.PubMed CentralPubMedGoogle Scholar
- Ding J, Yang L, Yan YT, Chen A, Desai N, Wynshaw-Boris A, Shen MM: Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo. Nature. 1998, 395 (6703): 702-707. 10.1038/27215.View ArticlePubMedGoogle Scholar
- Watanabe D, Suetake I, Tada T, Tajima S: Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mech Dev. 2002, 118 (1-2): 187-190. 10.1016/S0925-4773(02)00242-3.View ArticlePubMedGoogle Scholar
- Rosner MH, Vigano MA, Ozato K, Timmons PM, Poirier F, Rigby PW, Staudt LM: A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature. 1990, 345 (6277): 686-692. 10.1038/345686a0.View ArticlePubMedGoogle Scholar
- Grummer R, Reuss B, Winterhager E: Expression pattern of different gap junction connexins is related to embryo implantation. Int J Dev Biol. 1996, 40 (1): 361-367.PubMedGoogle Scholar
- Lin TP, Labosky PA, Grabel LB, Kozak CA, Pitman JL, Kleeman J, MacLeod CL: The Pem homeobox gene is X-linked and exclusively expressed in extraembryonic tissues during early murine development. Dev Biol. 1994, 166 (1): 170-179. 10.1006/dbio.1994.1305.View ArticlePubMedGoogle Scholar
- Lee JE, Pintar J, Efstratiadis A: Pattern of the insulin-like growth factor II gene expression during early mouse embryogenesis. Development. 1990, 110 (1): 151-159.PubMedGoogle Scholar
- Ellison JW, Ramos C, Yen PH, Shapiro LJ: Structure and expression of the human pseudoautosomal gene XE7. Hum Mol Genet. 1992, 1 (9): 691-696. 10.1093/hmg/1.9.782-a.View ArticlePubMedGoogle Scholar
- Ellison J, Passage M, Yu LC, Yen P, Mohandas TK, Shapiro L: Directed isolation of human genes that escape X inactivation. Somat Cell Mol Genet. 1992, 18 (3): 259-268. 10.1007/BF01233862.View ArticlePubMedGoogle Scholar
- Voland JR, Wyzykowski RJ, Huang M, Dutton RW: Cloning and sequencing of a trophoblast-endothelial-activated lymphocyte surface protein: cDNA sequence and genomic structure. Proc Natl Acad Sci U S A. 1992, 89 (21): 10425-10429. 10.1073/pnas.89.21.10425.PubMed CentralView ArticlePubMedGoogle Scholar
- Genomatix. [http://www.genomatix.de/]
- Chung S, Jiang L, Cheng S, Furneaux H: Purification and properties of HuD, a neuronal RNA-binding protein. J Biol Chem. 1996, 271 (19): 11518-11524. 10.1074/jbc.271.19.11163.View ArticlePubMedGoogle Scholar
- Wang X, Tanaka Hall TM: Structural basis for recognition of AU-rich element RNA by the HuD protein. Nat Struct Biol. 2001, 8 (2): 141-145. 10.1038/84131.View ArticlePubMedGoogle Scholar
- Ono R, Kobayashi S, Wagatsuma H, Aisaka K, Kohda T, Kaneko-Ishino T, Ishino F: A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21. Genomics. 2001, 73 (2): 232-237. 10.1006/geno.2001.6494.View ArticlePubMedGoogle Scholar
- Okita C, Meguro M, Hoshiya H, Haruta M, Sakamoto YK, Oshimura M: A new imprinted cluster on the human chromosome 7q21-q31, identified by human-mouse monochromosomal hybrids. Genomics. 2003, 81 (6): 556-559. 10.1016/S0888-7543(03)00052-1.View ArticlePubMedGoogle Scholar
- Ono R, Shiura H, Aburatani H, Kohda T, Kaneko-Ishino T, Ishino F: Identification of a large novel imprinted gene cluster on mouse proximal chromosome 6. Genome Res. 2003, 13 (7): 1696-1705. 10.1101/gr.906803.PubMed CentralView ArticlePubMedGoogle Scholar
- Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y: Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1. Cancer Res. 2003, 63 (12): 3043-3048.PubMedGoogle Scholar
- Bonthron DT, Hayward BE, Moran V, Strain L: Characterization of TH1 and CTSZ, two non-imprinted genes downstream of GNAS1 in chromosome 20q13. Hum Genet. 2000, 107 (2): 165-175. 10.1007/s004390000344.View ArticlePubMedGoogle Scholar
- Deussing J, von Olshausen I, Peters C: Murine and human cathepsin Z: cDNA-cloning, characterization of the genes and chromosomal localization. Biochim Biophys Acta. 2000, 1491 (1-3): 93-106.View ArticlePubMedGoogle Scholar
- Verroust PJ, Christensen EI: Megalin and cubilin--the story of two multipurpose receptors unfolds. Nephrol Dial Transplant. 2002, 17 (11): 1867-1871. 10.1093/ndt/17.11.1867.View ArticlePubMedGoogle Scholar
- Kozyraki R: Cubilin, a multifunctional epithelial receptor: an overview. J Mol Med. 2001, 79 (4): 161-167. 10.1007/s001090100193.View ArticlePubMedGoogle Scholar
- Meno C, Gritsman K, Ohishi S, Ohfuji Y, Heckscher E, Mochida K, Shimono A, Kondoh H, Talbot WS, Robertson EJ, Schier AF, Hamada H: Mouse Lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation. Mol Cell. 1999, 4 (3): 287-298. 10.1016/S1097-2765(00)80331-7.View ArticlePubMedGoogle Scholar
- Perea-Gomez A, Shawlot W, Sasaki H, Behringer RR, Ang S: HNF3beta and Lim1 interact in the visceral endoderm to regulate primitive streak formation and anterior-posterior polarity in the mouse embryo. Development. 1999, 126 (20): 4499-4511.PubMedGoogle Scholar
- Belo JA, Bouwmeester T, Leyns L, Kertesz N, Gallo M, Follettie M, De Robertis EM: Cerberus-like is a secreted factor with neutralizing activity expressed in the anterior primitive endoderm of the mouse gastrula. Mech Dev. 1997, 68 (1-2): 45-57. 10.1016/S0925-4773(97)00125-1.View ArticlePubMedGoogle Scholar
- Kimura-Yoshida C, Nakano H, Okamura D, Nakao K, Yonemura S, Belo JA, Aizawa S, Matsui Y, Matsuo I: Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm. Dev Cell. 2005, 9 (5): 639-650. 10.1016/j.devcel.2005.09.011.View ArticlePubMedGoogle Scholar
- Lu PJ, Sundquist K, Baeckstrom D, Poulsom R, Hanby A, Meier-Ewert S, Jones T, Mitchell M, Pitha-Rowe P, Freemont P, Taylor-Papadimitriou J: A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer. J Biol Chem. 1999, 274 (22): 15633-15645. 10.1074/jbc.274.22.15633.View ArticlePubMedGoogle Scholar
- Barrett A, Madsen B, Copier J, Lu PJ, Cooper L, Scibetta AG, Burchell J, Taylor-Papadimitriou J: PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen?. Int J Cancer. 2002, 101 (6): 581-588. 10.1002/ijc.10644.View ArticlePubMedGoogle Scholar
- Madsen B, Spencer-Dene B, Poulsom R, Hall D, Lu PJ, Scott K, Shaw AT, Burchell JM, Freemont P, Taylor-Papadimitriou J: Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer. Gene Expr Patterns. 2002, 2 (3-4): 275-282. 10.1016/S1567-133X(02)00051-0.View ArticlePubMedGoogle Scholar
- Tan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS: Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. J Biol Chem. 2003, 278 (23): 20507-20513. 10.1074/jbc.M301994200.View ArticlePubMedGoogle Scholar
- Shimono A, Okuda T, Kondoh H: N-myc-dependent repression of ndr1, a gene identified by direct subtraction of whole mouse embryo cDNAs between wild type and N-myc mutant. Mech Dev. 1999, 83 (1-2): 39-52. 10.1016/S0925-4773(99)00025-8.View ArticlePubMedGoogle Scholar
- van Belzen N, Dinjens WN, Diesveld MP, Groen NA, van der Made AC, Nozawa Y, Vlietstra R, Trapman J, Bosman FT: A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms. Lab Invest. 1997, 77 (1): 85-92.PubMedGoogle Scholar
- Piquemal D, Joulia D, Balaguer P, Basset A, Marti J, Commes T: Differential expression of the RTP/Drg1/Ndr1 gene product in proliferating and growth arrested cells. Biochim Biophys Acta. 1999, 1450 (3): 364-373. 10.1016/S0167-4889(99)00056-7.View ArticlePubMedGoogle Scholar
- Gomez-Casero E, Navarro M, Rodriguez-Puebla ML, Larcher F, Paramio JM, Conti CJ, Jorcano JL: Regulation of the differentiation-related gene Drg-1 during mouse skin carcinogenesis. Mol Carcinog. 2001, 32 (2): 100-109. 10.1002/mc.1069.View ArticlePubMedGoogle Scholar
- van Lohuizen M: Functional analysis of mouse Polycomb group genes. Cell Mol Life Sci. 1998, 54 (1): 71-79. 10.1007/s000180050126.View ArticlePubMedGoogle Scholar
- Schumacher A, Magnuson T: Murine Polycomb- and trithorax-group genes regulate homeotic pathways and beyond. Trends Genet. 1997, 13 (5): 167-170. 10.1016/S0168-9525(97)01133-5.View ArticlePubMedGoogle Scholar
- Gould A: Functions of mammalian Polycomb group and trithorax group related genes. Curr Opin Genet Dev. 1997, 7 (4): 488-494. 10.1016/S0959-437X(97)80075-5.View ArticlePubMedGoogle Scholar
- Usui H, Ichikawa T, Kobayashi K, Kumanishi T: Cloning of a novel murine gene Sfmbt, Scm-related gene containing four mbt domains, structurally belonging to the Polycomb group of genes. Gene. 2000, 248 (1-2): 127-135. 10.1016/S0378-1119(00)00131-1.View ArticlePubMedGoogle Scholar
- Liptau H, Viebahn C: Expression patterns of gap junctional proteins connexin 32 and 43 suggest new communication compartments in the gastrulating rabbit embryo. Differentiation. 1999, 65 (4): 209-219. 10.1046/j.1432-0436.1999.6540209.x.View ArticlePubMedGoogle Scholar
- Dahl E, Winterhager E, Reuss B, Traub O, Butterweck A, Willecke K: Expression of the gap junction proteins connexin31 and connexin43 correlates with communication compartments in extraembryonic tissues and in the gastrulating mouse embryo, respectively. J Cell Sci. 1996, 109 ( Pt 1): 191-197.Google Scholar
- Davies TC, Barr KJ, Jones DH, Zhu D, Kidder GM: Multiple members of the connexin gene family participate in preimplantation development of the mouse. Dev Genet. 1996, 18 (3): 234-243. 10.1002/(SICI)1520-6408(1996)18:3<234::AID-DVG4>3.0.CO;2-A.View ArticlePubMedGoogle Scholar
- Kimura C, Shen MM, Takeda N, Aizawa S, Matsuo I: Complementary functions of Otx2 and Cripto in initial patterning of mouse epiblast. Dev Biol. 2001, 235 (1): 12-32. 10.1006/dbio.2001.0289.View ArticlePubMedGoogle Scholar
- Perea-Gomez A, Lawson KA, Rhinn M, Zakin L, Brulet P, Mazan S, Ang SL: Otx2 is required for visceral endoderm movement and for the restriction of posterior signals in the epiblast of the mouse embryo. Development. 2001, 128 (5): 753-765.PubMedGoogle Scholar
- Perea-Gomez A, Vella FD, Shawlot W, Oulad-Abdelghani M, Chazaud C, Meno C, Pfister V, Chen L, Robertson E, Hamada H, Behringer RR, Ang SL: Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. Dev Cell. 2002, 3 (5): 745-756. 10.1016/S1534-5807(02)00321-0.View ArticlePubMedGoogle Scholar
- Kimura C, Yoshinaga K, Tian E, Suzuki M, Aizawa S, Matsuo I: Visceral endoderm mediates forebrain development by suppressing posteriorizing signals. Dev Biol. 2000, 225 (2): 304-321. 10.1006/dbio.2000.9835.View ArticlePubMedGoogle Scholar
- Varlet I, Collignon J, Robertson EJ: nodal expression in the primitive endoderm is required for specification of the anterior axis during mouse gastrulation. Development. 1997, 124 (5): 1033-1044.PubMedGoogle Scholar
- Brennan J, Lu CC, Norris DP, Rodriguez TA, Beddington RS, Robertson EJ: Nodal signalling in the epiblast patterns the early mouse embryo. Nature. 2001, 411 (6840): 965-969. 10.1038/35082103.View ArticlePubMedGoogle Scholar
- Perea-Gomez A, Vella FD, Shawlot W, Oulad-Abdelghani M, Chazaud C, Meno C, Pfister V, Chen L, Robertson E, Hamada H, et al: Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. Dev Cell. 2002, 3: 745-756. 10.1016/S1534-5807(02)00321-0.View ArticlePubMedGoogle Scholar
- Ralston A, Rossant J: How signaling promotes stem cell survival: trophoblast stem cells and Shp2. Dev Cell. 2006, 10 (3): 275-276. 10.1016/j.devcel.2006.02.007.View ArticlePubMedGoogle Scholar
- Ciruna BG, Rossant J: Expression of the T-box gene Eomesodermin during early mouse development. Mech Dev. 1999, 81 (1-2): 199-203. 10.1016/S0925-4773(98)00243-3.View ArticlePubMedGoogle Scholar
- Coucouvanis E, Martin GR: BMP signaling plays a role in visceral endoderm differentiation and cavitation in the early mouse embryo. Development. 1999, 126 (3): 535-546.PubMedGoogle Scholar
- Zhao SH, Simmons DG, Cross JC, Scheetz TE, Casavant TL, Soares MB, Tuggle CK: PLET1 (C11orf34), a highly expressed and processed novel gene in pig and mouse placenta, is transcribed but poorly spliced in human. Genomics. 2004, 84 (1): 114-125. 10.1016/j.ygeno.2004.02.006.View ArticlePubMedGoogle Scholar
- Zhao SH, Tuggle CK: Linkage mapping and expression analyses of a novel gene, placentally expressed transcript 1 (PLET1) in the pig. Anim Genet. 2004, 35 (1): 72-74. 10.1046/j.0268-9146.2003.01075.x.View ArticlePubMedGoogle Scholar
- Akamatsu W, Fujihara H, Mitsuhashi T, Yano M, Shibata S, Hayakawa Y, Okano HJ, Sakakibara S, Takano H, Takano T, Takahashi T, Noda T, Okano H: The RNA-binding protein HuD regulates neuronal cell identity and maturation. Proc Natl Acad Sci U S A. 2005, 102 (12): 4625-4630. 10.1073/pnas.0407523102.PubMed CentralView ArticlePubMedGoogle Scholar
- Smith L, Underhill P, Pritchard C, Tymowska-Lalanne Z, Abdul-Hussein S, Hilton H, Winchester L, Williams D, Freeman T, Webb S, Greenfield A: Single primer amplification (SPA) of cDNA for microarray expression analysis. Nucleic Acids Res. 2003, 31 (3): e9-10.1093/nar/gng009.PubMed CentralView ArticlePubMedGoogle Scholar
- Tanaka TS, Jaradat SA, Lim MK, Kargul GJ, Wang X, Grahovac MJ, Pantano S, Sano Y, Piao Y, Nagaraja R, Doi H, Wood WH, Becker KG, Ko MS: Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc Natl Acad Sci U S A. 2000, 97 (16): 9127-9132. 10.1073/pnas.97.16.9127.PubMed CentralView ArticlePubMedGoogle Scholar
- Laboratory of Genetics, NIA/NIH Mouse Genomics. [http://lgsun.grc.nia.nih.gov]
- Wilkinson DG, Nieto MA: Detection of messenger RNA by in situ hybridization to tissue sections and whole mounts. Methods Enzymol. 1993, 225: 361-373.View ArticlePubMedGoogle Scholar
- Kelley LA, Maccallum R, Sternberg MJE: RECOMB 99, Proceedings of the Third Annual Conference on Computational Molecular Biology. Edited by: Istrail S, Pevzner P, Waterman M. 1999, The Association for Computing Machinery, New York, New York 10036, 218-225.View ArticleGoogle Scholar
- 3D-PSSM. [http://www.sbg.bio.ic.ac.uk/servers/3dpssm/]
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.