title: TBX3 Directs Cell-Fate Decision toward Mesendoderm.
abstract: Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.
authors: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany ; International Graduate School in Molecular Medicine, Ulm University, 89081 Ulm, Germany.
authors: Clair E
authors: CE
authors: Weidgang
authors: Ronan
authors: R
authors: Russell
authors: Purushothama R
authors: PR
authors: Tata
authors: Susanne J
authors: SJ
authors: Kühl
authors: Anett
authors: A
authors: Illing
authors: Martin
authors: M
authors: Müller
authors: Qiong
authors: Q
authors: Lin
authors: Cornelia
authors: C
authors: Brunner
authors: Tobias M
authors: TM
authors: Boeckers
authors: Kerstin
authors: K
authors: Bauer
authors: Apriliana E R
authors: AE
authors: Kartikasari
authors: Yanchun
authors: Y
authors: Guo
authors: Melanie
authors: M
authors: Radenz
authors: Christof
authors: C
authors: Bernemann
authors: Matthias
authors: M
authors: Weiß
authors: Thomas
authors: T
authors: Seufferlein
authors: Martin
authors: M
authors: Zenke
authors: Michelina
authors: M
authors: Iacovino
authors: Michael
authors: M
authors: Kyba
authors: Hans R
authors: HR
authors: Schöler
authors: Michael
authors: M
authors: Kühl
authors: Stefan
authors: S
authors: Liebau
authors: Alexander
authors: A
authors: Kleger
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology*; D054262:Gastrulation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008648:Mesoderm / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D055457:Nodal Protein / Q000096:biosynthesis / Q000235:genetics; D051899:Smad2 Protein / Q000235:genetics; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D014981:Xenopus
chemical_list: D055457:Nodal Protein; C526008:Nodal protein, mouse; D051899:Smad2 Protein; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse