{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:16:11Z","timestamp":1790777771068,"version":"4.1.0"},"reference-count":45,"publisher":"The Company of Biologists","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,15]]},"abstract":"<jats:p>The labyrinth of the rodent placenta contains villi that are the site of nutrient exchange between mother and fetus. They are covered by three trophoblast cell types that separate the maternal blood sinusoids from fetal capillaries - a single mononuclear cell that is a subtype of trophoblast giant cell (sinusoidal or S-TGC) with endocrine function and two multinucleated syncytiotrophoblast layers, each resulting from cell-cell fusion, that function in nutrient transport. The developmental origins of these cell types have not previously been elucidated. We report here the discovery of cell-layer-restricted genes in the mid-gestation labyrinth (E12.5-14.5)including Ctsq in S-TGCs (also Hand1-positive), Syna in syncytiotrophoblast layer I (SynT-I), and Gcm1,Cebpa and Synb in syncytiotrophoblast layer II (SynT-II). These genes were also expressed in distinct layers in the chorion as early as E8.5,prior to villous formation. Specifically, Hand1 was expressed in apical cells lining maternal blood spaces (Ctsq is not expressed until E12.5), Syna in a layer immediately below, and Gcm1,Cebpa and Synb in basal cells in contact with the allantois. Cebpa and Synb were co-expressed with Gcm1 and were reduced in Gcm1 mutants. By contrast, Hand1 and Syna expression was unaltered in Gcm1 mutants, suggesting that Gcm1-positive cells are not required for the induction of the other chorion layers. These data indicate that the three differentiated trophoblast cell types in the labyrinth arise from distinct and autonomous precursors in the chorion that are patterned before morphogenesis begins.<\/jats:p>","DOI":"10.1242\/dev.020099","type":"journal-article","created":{"date-parts":[[2008,4,30]],"date-time":"2008-04-30T20:54:09Z","timestamp":1209588849000},"page":"2083-2091","source":"Crossref","is-referenced-by-count":243,"title":["Early patterning of the chorion leads to the trilaminar trophoblast cell structure in the placental labyrinth"],"prefix":"10.1242","volume":"135","author":[{"given":"David G.","family":"Simmons","sequence":"first","affiliation":[{"name":"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, The University of Calgary, 3330 Hospital Drive NW,Calgary, AB, T2N 4N1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R. C.","family":"Natale","sequence":"additional","affiliation":[{"name":"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, The University of Calgary, 3330 Hospital Drive NW,Calgary, AB, T2N 4N1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Begay","sequence":"additional","affiliation":[{"name":"Max Delbrueck Center for Molecular Medicine, Robert-Roessle-Str. 10, 13092 Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, The University of Calgary, 3330 Hospital Drive NW,Calgary, AB, T2N 4N1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Leutz","sequence":"additional","affiliation":[{"name":"Max Delbrueck Center for Molecular Medicine, Robert-Roessle-Str. 10, 13092 Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Cross","sequence":"additional","affiliation":[{"name":"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, The University of Calgary, 3330 Hospital Drive NW,Calgary, AB, T2N 4N1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042621121719700_REF1","doi-asserted-by":"crossref","unstructured":"Akiyama, Y., Hosoya, T., Poole, A. M. and Hotta, Y.(1996). The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. Proc. Natl. Acad. Sci. USA93,14912-14916.","DOI":"10.1073\/pnas.93.25.14912"},{"key":"2021042621121719700_REF2","doi-asserted-by":"crossref","unstructured":"Anson-Cartwright, L., Dawson, K., Holmyard, D., Fisher, S. J.,Lazzarini, R. A. and Cross, J. C. (2000). The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta. Nat. Genet.25,311-314.","DOI":"10.1038\/77076"},{"key":"2021042621121719700_REF3","doi-asserted-by":"crossref","unstructured":"Basyuk, E., Cross, J. C., Corbin, J., Nakayama, H., Hunter, P.,Nait-Oumesmar, B. and Lazzarini, R. A. (1999). Murine Gcm1 gene is expressed in a subset of placental trophoblast cells. Dev. Dyn.214,303-311.","DOI":"10.1002\/(SICI)1097-0177(199904)214:4<303::AID-AJA3>3.0.CO;2-B"},{"key":"2021042621121719700_REF4","doi-asserted-by":"crossref","unstructured":"Beck, F., Erler, T., Russell, A. and James, R.(1995). Expression of Cdx-2 in the mouse embryo and placenta:possible role in patterning of the extra-embryonic membranes. Dev. Dyn.204,219-227.","DOI":"10.1002\/aja.1002040302"},{"key":"2021042621121719700_REF5","doi-asserted-by":"crossref","unstructured":"Begay, V., Smink, J. and Leutz, A. (2004). Essential requirement of CCAAT\/enhancer binding proteins in embryogenesis. Mol. Cell. Biol.24,9744-9751.","DOI":"10.1128\/MCB.24.22.9744-9751.2004"},{"key":"2021042621121719700_REF6","doi-asserted-by":"crossref","unstructured":"Berghorn, K. A., Clark, P. A., Encarnacion, B., Deregis, C. J.,Folger, J. K., Morasso, M. I., Soares, M. J., Wolfe, M. W. and Roberson, M. S. (2005). Developmental expression of the homeobox protein Distal-less 3 and its relationship to progesterone production in mouse placenta. J. Endocrinol.186,315-323.","DOI":"10.1677\/joe.1.06217"},{"key":"2021042621121719700_REF7","doi-asserted-by":"crossref","unstructured":"Campbell, W. J., Deb, S., Kwok, S. C., Joslin, J. A. and Soares,M. J. (1989). Differential expression of placental lactogen-II and prolactin-like protein-A in the rat chorioallantoic placenta. Endocrinology125,1565-1574.","DOI":"10.1210\/endo-125-3-1565"},{"key":"2021042621121719700_REF8","doi-asserted-by":"crossref","unstructured":"Chang, C. W., Chuang, H. C., Yu, C., Yao, T. P. and Chen, H.(2005). Stimulation of GCMa transcriptional activity by cyclic AMP\/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa. Mol. Cell. Biol.25,8401-8414.","DOI":"10.1128\/MCB.25.19.8401-8414.2005"},{"key":"2021042621121719700_REF9","doi-asserted-by":"crossref","unstructured":"Church, G. M. and Gilbert, W. (1984). Genomic sequencing. Proc. Natl. Acad. Sci. USA81,1991-1995.","DOI":"10.1073\/pnas.81.7.1991"},{"key":"2021042621121719700_REF10","doi-asserted-by":"crossref","unstructured":"Coan, P. M., Ferguson-Smith, A. C. and Burton, G. J.(2005). Ultrastructural changes in the interhaemal membrane and junctional zone of the murine chorioallantoic placenta across gestation. J. Anat.207,783-796.","DOI":"10.1111\/j.1469-7580.2005.00488.x"},{"key":"2021042621121719700_REF11","doi-asserted-by":"crossref","unstructured":"Cross, J. C. (2000). Genetic insights into trophoblast differentiation and placental morphogenesis. Semin. Cell Dev. Biol.11,105-113.","DOI":"10.1006\/scdb.2000.0156"},{"key":"2021042621121719700_REF12","doi-asserted-by":"crossref","unstructured":"Cross, J. C., Nakano, H., Natale, D. R., Simmons, D. G. and Watson, E. D. (2006). Branching morphogenesis during development of placental villi. Differentiation74,393-401.","DOI":"10.1111\/j.1432-0436.2006.00103.x"},{"key":"2021042621121719700_REF13","doi-asserted-by":"crossref","unstructured":"Dai, G., Wang, D., Liu, B., Kasik, J. W., Muller, H., White, R. A., Hummel, G. S. and Soares, M. J. (2000). Three novel paralogs of the rodent prolactin gene family. J. Endocrinol.166,63-75.","DOI":"10.1677\/joe.0.1660063"},{"key":"2021042621121719700_REF14","doi-asserted-by":"crossref","unstructured":"Davies, J. and Glasser, S. R. (1968). Histological and fine structural observations on the placenta of the rat. Acta Anat. Basel69,542-608.","DOI":"10.1159\/000143100"},{"key":"2021042621121719700_REF15","doi-asserted-by":"crossref","unstructured":"Deb, S., Faria, T. N., Roby, K. F., Larsen, D., Kwok, S. C.,Talamantes, F. and Soares, M. J. (1991). Identification and characterization of a new member of the prolactin family, placental lactogen-I variant. J. Biol. Chem.266,1605-1610.","DOI":"10.1016\/S0021-9258(18)52337-1"},{"key":"2021042621121719700_REF16","doi-asserted-by":"crossref","unstructured":"Dupressoir, A., Marceau, G., Vernochet, C., Benit, L.,Kanellopoulos, C., Sapin, V. and Heidmann, T. (2005). Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae. Proc. Natl. Acad. Sci. USA102,725-730.","DOI":"10.1073\/pnas.0406509102"},{"key":"2021042621121719700_REF17","doi-asserted-by":"crossref","unstructured":"Enders, A. C. (1965). A comparative study of the fine structure of the trophoblast in several hemochorial placentas. Am. J. Anat.116,29-67.","DOI":"10.1002\/aja.1001160103"},{"key":"2021042621121719700_REF18","doi-asserted-by":"crossref","unstructured":"Hancock, S. N., Agulnik, S. I., Silver, L. M. and Papaioannou,V. E. (1999). Mapping and expression analysis of the mouse ortholog of Xenopus Eomesodermin. Mech. Dev.81,205-208.","DOI":"10.1016\/S0925-4773(98)00244-5"},{"key":"2021042621121719700_REF19","doi-asserted-by":"crossref","unstructured":"Hemberger, M. and Cross, J. C. (2001). Genes governing placental development. Trends Endocrinol. Metab.12,162-168.","DOI":"10.1016\/S1043-2760(01)00375-7"},{"key":"2021042621121719700_REF20","doi-asserted-by":"crossref","unstructured":"Hernandez-Verdun, D. (1974). Morphogenesis of the syncytium in the mouse placenta. Ultrastructural study. Cell Tissue Res.148,381-396.","DOI":"10.1007\/BF00224265"},{"key":"2021042621121719700_REF21","doi-asserted-by":"crossref","unstructured":"Hughes, M., Dobric, N., Scott, I. C., Su, L., Starovic, M.,St-Pierre, B., Egan, S. E., Kingdom, J. C. and Cross, J. C.(2004). The Hand1, Stra13 and Gcm1 transcription factors override FGF signaling to promote terminal differentiation of trophoblast stem cells. Dev. Biol.271,362-371.","DOI":"10.1016\/j.ydbio.2004.03.029"},{"key":"2021042621121719700_REF22","doi-asserted-by":"crossref","unstructured":"Ishida, M., Ono, K., Taguchi, S., Ohashi, S., Naito, J.,Horiguchi, K. and Harigaya, T. (2004). Cathepsin gene expression in mouse placenta during the latter half of pregnancy. J. Reprod. Dev.50,515-523.","DOI":"10.1262\/jrd.50.515"},{"key":"2021042621121719700_REF23","doi-asserted-by":"crossref","unstructured":"Jacquemin, P., Sapin, V., Alsat, E., Evain-Brion, D., Dolle, P. and Davidson, I. (1998). Differential expression of the TEF family of transcription factors in the murine placenta and during differentiation of primary human trophoblasts in vitro. Dev. Dyn.212,423-436.","DOI":"10.1002\/(SICI)1097-0177(199807)212:3<423::AID-AJA10>3.0.CO;2-1"},{"key":"2021042621121719700_REF24","doi-asserted-by":"crossref","unstructured":"Jollie, W. P. (1964). Fine structural changes in placental labyrinth of the rat with increasing gestational age. J. Ultrastruct. Res.10,27-47.","DOI":"10.1016\/S0022-5320(64)90018-8"},{"key":"2021042621121719700_REF25","doi-asserted-by":"crossref","unstructured":"Lee, C. K., Moon, D. H., Shin, C. S., Kim, H., Yoon, Y. D.,Kang, H. S., Lee, B. J. and Kang, S. G. (2003). Circadian expression of Mel1a and PL-II genes in placenta: effects of melatonin on the PL-II gene expression in the rat placenta. Mol. Cell. Endocrinol.200,57-66.","DOI":"10.1016\/S0303-7207(02)00414-8"},{"key":"2021042621121719700_REF26","doi-asserted-by":"crossref","unstructured":"Li, Y., Lemaire, P. and Behringer, R. R.(1997). Esx1, a novel X chromosome-linked homeobox gene expressed in mouse extraembryonic tissues and male germ cells. Dev. Biol.188,85-95.","DOI":"10.1006\/dbio.1997.8640"},{"key":"2021042621121719700_REF27","doi-asserted-by":"crossref","unstructured":"Mo, F., Muntean, A. G., Chen, C., Stolz, D. B., Watkins, S. C. and Lau, L. F. (2002). CYR61 (CCN1) is essential for placental development and vascular integrity. Mol. Cell. Biol.22,8709-8720.","DOI":"10.1128\/MCB.22.24.8709-8720.2002"},{"key":"2021042621121719700_REF28","doi-asserted-by":"crossref","unstructured":"Morasso, M. I., Grinberg, A., Robinson, G., Sargent, T. D. and Mahon, K. A. (1999). Placental failure in mice lacking the homeobox gene Dlx3. Proc. Natl. Acad. Sci. USA96,162-167.","DOI":"10.1073\/pnas.96.1.162"},{"key":"2021042621121719700_REF29","doi-asserted-by":"crossref","unstructured":"Pettersson, K., Svensson, K., Mattsson, R., Carlsson, B.,Ohlsson, R. and Berkenstam, A. (1996). Expression of a novel member of estrogen response element-binding nuclear receptors is restricted to the early stages of chorion formation during mouse embryogenesis. Mech. Dev.54,211-223.","DOI":"10.1016\/0925-4773(95)00479-3"},{"key":"2021042621121719700_REF30","doi-asserted-by":"crossref","unstructured":"Rossant, J. and Cross, J. C. (2001). Placental development: lessons from mouse mutants. Nat. Rev. Genet.2,538-548.","DOI":"10.1038\/35080570"},{"key":"2021042621121719700_REF31","doi-asserted-by":"crossref","unstructured":"Sahgal, N., Knipp, G. T., Liu, B., Chapman, B. M., Dai, G. and Soares, M. J. (2000). Identification of two new nonclassical members of the rat prolactin family. J. Mol. Endocrinol.24,95-108.","DOI":"10.1677\/jme.0.0240095"},{"key":"2021042621121719700_REF32","doi-asserted-by":"crossref","unstructured":"Schreiber, J., Sock, E. and Wegner, M. (1997). The regulator of early gliogenesis glial cells missing is a transcription factor with a novel type of DNA-binding domain. Proc. Natl. Acad. Sci. USA94,4739-4744.","DOI":"10.1073\/pnas.94.9.4739"},{"key":"2021042621121719700_REF33","doi-asserted-by":"crossref","unstructured":"Schreiber, J., Riethmacher-Sonnenberg, E., Riethmacher, D.,Tuerk, E. E., Enderich, J., Bosl, M. R. and Wegner, M.(2000). Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa. Mol. Cell. Biol.20,2466-2474.","DOI":"10.1128\/MCB.20.7.2466-2474.2000"},{"key":"2021042621121719700_REF34","doi-asserted-by":"crossref","unstructured":"Schubert, S. W., Kardash, E., Khan, M. A., Cheusova, T., Kilian,K., Wegner, M. and Hashemolhosseini, S. (2004). Interaction,cooperative promoter modulation, and renal colocalization of GCMa and Pitx2. J. Biol. Chem.279,50358-50365.","DOI":"10.1074\/jbc.M404587200"},{"key":"2021042621121719700_REF35","doi-asserted-by":"crossref","unstructured":"Scott, I. C., Anson-Cartwright, L., Riley, P., Reda, D. and Cross, J. C. (2000). The HAND1 basic helix-loop-helix transcription factor regulates trophoblast differentiation via multiple mechanisms. Mol. Cell. Biol.20,530-541.","DOI":"10.1128\/MCB.20.2.530-541.2000"},{"key":"2021042621121719700_REF36","doi-asserted-by":"crossref","unstructured":"Simmons, D. G. and Cross, J. C. (2005). Determinants of trophoblast lineage and cell subtype specification in the mouse placenta. Dev. Biol.284, 12-24.","DOI":"10.1016\/j.ydbio.2005.05.010"},{"key":"2021042621121719700_REF37","doi-asserted-by":"crossref","unstructured":"Simmons, D. G., Fortier, A. L. and Cross, J. C.(2007). Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta. Dev. Biol. 304,567-578.","DOI":"10.1016\/j.ydbio.2007.01.009"},{"key":"2021042621121719700_REF38","unstructured":"Snell, G. D. and Stevens, L. C. (1966). Early embryology. In Biology of the Laboratory Mouse (ed. E. L. Green), pp. 205-245. New York:McGraw-Hill."},{"key":"2021042621121719700_REF39","doi-asserted-by":"crossref","unstructured":"Steingrimsson, E., Tessarollo, L., Reid, S. W., Jenkins, N. A. and Copeland, N. G. (1998). The bHLH-Zip transcription factor Tfeb is essential for placental vascularization. Development125,4607-4616.","DOI":"10.1242\/dev.125.23.4607"},{"key":"2021042621121719700_REF40","doi-asserted-by":"crossref","unstructured":"Susens, U., Aguiluz, J. B., Evans, R. M. and Borgmeyer, U.(1997). The germ cell nuclear factor mGCNF is expressed in the developing nervous system. Dev. Neurosci.19,410-420.","DOI":"10.1159\/000111238"},{"key":"2021042621121719700_REF41","doi-asserted-by":"crossref","unstructured":"Tanaka, S., Kunath, T., Hadjantonakis, A. K., Nagy, A. and Rossant, J. (1998). Promotion of trophoblast stem cell proliferation by FGF4. Science282,2072-2075.","DOI":"10.1126\/science.282.5396.2072"},{"key":"2021042621121719700_REF42","doi-asserted-by":"crossref","unstructured":"Tompers, D. M., Foreman, R. K., Wang, Q., Kumanova, M. and Labosky, P. A. (2005). Foxd3 is required in the trophoblast progenitor cell lineage of the mouse embryo. Dev. Biol.285,126-137.","DOI":"10.1016\/j.ydbio.2005.06.008"},{"key":"2021042621121719700_REF43","doi-asserted-by":"crossref","unstructured":"Uy, G. D., Downs, K. M. and Gardner, R. L.(2002). Inhibition of trophoblast stem cell potential in chorionic ectoderm coincides with occlusion of the ectoplacental cavity in the mouse. Development129,3913-3924.","DOI":"10.1242\/dev.129.16.3913"},{"key":"2021042621121719700_REF44","unstructured":"Voss, A. K., Thomas, T. and Gruss, P. (2000). Mice lacking HSP90beta fail to develop a placental labyrinth. Development127,1-11."},{"key":"2021042621121719700_REF45","doi-asserted-by":"crossref","unstructured":"Watson, E. D. and Cross, J. C. (2005). Development of structures and transport functions in the mouse placenta. Physiology Bethesda20,180-193.","DOI":"10.1152\/physiol.00001.2005"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/135\/12\/2083\/1156726\/2083.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/135\/12\/2083\/1156726\/2083.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T21:33:27Z","timestamp":1684359207000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/135\/12\/2083\/64739\/Early-patterning-of-the-chorion-leads-to-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,15]]},"references-count":45,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2008,6,15]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.020099","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2008,6,15]]}}}