Distinct Mechanisms Regulate Cdx2 Expression in the Blastocyst and in Trophoblast Stem Cells

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jun 4

PMID 27256674

Citations 10

Authors

Teresa Rayon

Sergio Menchero

Isabel Rollan

Inmaculada Ors

Anne Helness

Miguel Crespo

Andres Nieto

Veronique Azuara

Janet Rossant

Miguel Manzanares

Affiliations

Soon will be listed here.

Abstract

The first intercellular differences during mammalian embryogenesis arise in the blastocyst, producing the inner cell mass and the trophectoderm. The trophectoderm is the first extraembryonic tissue and does not contribute to the embryo proper, its differentiation instead forming tissues that sustain embryonic development. Crucial roles in extraembryonic differentiation have been identified for certain transcription factors, but a comprehensive picture of the regulation of this early specification is still lacking. Here, we investigated whether the regulatory mechanisms involved in Cdx2 expression in the blastocyst are also utilized in the postimplantation embryo. We analyzed an enhancer that is regulated through Hippo and Notch in the blastocyst trophectoderm, unexpectedly finding that it is inactive in the extraembryonic structures at postimplantation stages. Further analysis identified other Cdx2 regulatory elements including a stem-cell specific regulatory sequence and an element that drives reporter expression in the trophectoderm, a subset of cells in the extraembryonic region of the postimplantation embryo and in trophoblast stem cells. The cross-comparison in this study of cis-regulatory elements employed in the blastocyst, stem cell populations and the postimplantation embryo provides new insights into early mammalian development and suggests a two-step mechanism in Cdx2 regulation.

Citing Articles

Early developmental plasticity enables the induction of an intermediate extraembryonic cell state.

Sathyanarayanan A, Ing-Simmons E, Chen R, Jeong H, Ozguldez H, Fan R Sci Adv. 2022; 8(44):eabl9583.

PMID: 36332016 PMC: 9635831. DOI: 10.1126/sciadv.abl9583.

Embryonic and extraembryonic tissues during mammalian development: shifting boundaries in time and space.

Thowfeequ S, Srinivas S Philos Trans R Soc Lond B Biol Sci. 2022; 377(1865):20210255.

PMID: 36252217 PMC: 9574638. DOI: 10.1098/rstb.2021.0255.

Molecular regulation of trophoblast stem cell self-renewal and giant cell differentiation by the Hippo components YAP and LATS1.

Basak T, Ain R Stem Cell Res Ther. 2022; 13(1):189.

PMID: 35526072 PMC: 9080189. DOI: 10.1186/s13287-022-02844-w.

CDX2 downregulation in mouse mural trophectoderm during peri-implantation is heteronomous, dependent on the YAP-TEAD pathway and controlled by estrogen-induced factors.

Suzuki D, Okura K, Nagakura S, Ogawa H Reprod Med Biol. 2022; 21(1):e12446.

PMID: 35386376 PMC: 8967280. DOI: 10.1002/rmb2.12446.

Reprogrammed Bat Stem Cells as A Model to Study Host-Pathogen Interaction during Infection.

Aurine N, Baquerre C, Gaudino M, Jean C, Dumont C, Rival-Gervier S Microorganisms. 2021; 9(12).

PMID: 34946167 PMC: 8706405. DOI: 10.3390/microorganisms9122567.

References

Dietrich J, Hiiragi T . Stochastic patterning in the mouse pre-implantation embryo. Development. 2007; 134(23):4219-31. DOI: 10.1242/dev.003798. View

Wang W, Shashikant C . Evidence for positive and negative regulation of the mouse Cdx2 gene. J Exp Zool B Mol Dev Evol. 2007; 308(3):308-21. DOI: 10.1002/jez.b.21154. View

Shen Y, Yue F, McCleary D, Ye Z, Edsall L, Kuan S . A map of the cis-regulatory sequences in the mouse genome. Nature. 2012; 488(7409):116-20. PMC: 4041622. DOI: 10.1038/nature11243. View

Nowotschin S, Xenopoulos P, Schrode N, Hadjantonakis A . A bright single-cell resolution live imaging reporter of Notch signaling in the mouse. BMC Dev Biol. 2013; 13:15. PMC: 3663770. DOI: 10.1186/1471-213X-13-15. View

Watts J, Zhang C, Klein-Szanto A, Kormish J, Fu J, Zhang M . Study of FoxA pioneer factor at silent genes reveals Rfx-repressed enhancer at Cdx2 and a potential indicator of esophageal adenocarcinoma development. PLoS Genet. 2011; 7(9):e1002277. PMC: 3174211. DOI: 10.1371/journal.pgen.1002277. View

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A . Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7):RESEARCH0034. PMC: 126239. DOI: 10.1186/gb-2002-3-7-research0034. View

Nishioka N, Inoue K, Adachi K, Kiyonari H, Ota M, Ralston A . The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev Cell. 2009; 16(3):398-410. DOI: 10.1016/j.devcel.2009.02.003. View

Yamanaka Y, Ralston A, Stephenson R, Rossant J . Cell and molecular regulation of the mouse blastocyst. Dev Dyn. 2006; 235(9):2301-14. DOI: 10.1002/dvdy.20844. View

Benchetrit H, Herman S, van Wietmarschen N, Wu T, Makedonski K, Maoz N . Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells. Cell Stem Cell. 2015; 17(5):543-56. DOI: 10.1016/j.stem.2015.08.006. View

10.

Yoshimizu T, Sugiyama N, De Felice M, Yeom Y, Ohbo K, Masuko K . Germline-specific expression of the Oct-4/green fluorescent protein (GFP) transgene in mice. Dev Growth Differ. 2000; 41(6):675-84. DOI: 10.1046/j.1440-169x.1999.00474.x. View

11.

Ralston A, Cox B, Nishioka N, Sasaki H, Chea E, Rugg-Gunn P . Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2. Development. 2010; 137(3):395-403. DOI: 10.1242/dev.038828. View

12.

Rayon T, Menchero S, Nieto A, Xenopoulos P, Crespo M, Cockburn K . Notch and hippo converge on Cdx2 to specify the trophectoderm lineage in the mouse blastocyst. Dev Cell. 2014; 30(4):410-22. PMC: 4146744. DOI: 10.1016/j.devcel.2014.06.019. View

13.

Mak W, Baxter J, Silva J, Newall A, Otte A, Brockdorff N . Mitotically stable association of polycomb group proteins eed and enx1 with the inactive x chromosome in trophoblast stem cells. Curr Biol. 2002; 12(12):1016-20. DOI: 10.1016/s0960-9822(02)00892-8. View

14.

Nishioka N, Yamamoto S, Kiyonari H, Sato H, Sawada A, Ota M . Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos. Mech Dev. 2007; 125(3-4):270-83. DOI: 10.1016/j.mod.2007.11.002. View

15.

Rossant J, Tam P . Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse. Development. 2009; 136(5):701-13. DOI: 10.1242/dev.017178. View

16.

Ang S, Wierda A, Wong D, STEVENS K, Cascio S, Rossant J . The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development. 1993; 119(4):1301-15. DOI: 10.1242/dev.119.4.1301. View

17.

Kubaczka C, Senner C, Arauzo-Bravo M, Sharma N, Kuckenberg P, Becker A . Derivation and maintenance of murine trophoblast stem cells under defined conditions. Stem Cell Reports. 2014; 2(2):232-42. PMC: 3923226. DOI: 10.1016/j.stemcr.2013.12.013. View

18.

Marson A, Levine S, Cole M, Frampton G, Brambrink T, Johnstone S . Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell. 2008; 134(3):521-33. PMC: 2586071. DOI: 10.1016/j.cell.2008.07.020. View

19.

Kubaczka C, Senner C, Cierlitza M, Arauzo-Bravo M, Kuckenberg P, Peitz M . Direct Induction of Trophoblast Stem Cells from Murine Fibroblasts. Cell Stem Cell. 2015; 17(5):557-68. DOI: 10.1016/j.stem.2015.08.005. View

20.

Cockburn K, Rossant J . Making the blastocyst: lessons from the mouse. J Clin Invest. 2010; 120(4):995-1003. PMC: 2846056. DOI: 10.1172/JCI41229. View