T‐box genes in early embryogenesis

Showell, Chris; Binder, Olav; Conlon, Frank L.

doi:10.1002/dvdy.10480

Cited by 271 publications

(242 citation statements)

References 144 publications

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“…We detected 70 down-regulated and 53 up-regulated functional Brachyury target genes. Thus, it is likely that, although Brachyury targets a large number (1,942) of genes in the genome, only a small fraction of targeted genes showed gene-activation dependence on Brachyury, consistent with the previous observation that only 81 genes of ∼1,400 targeted genes are dependent of Xbra in Xenopus (12).…”

Section: Brachyury Coordinates Gene Expression During In Vitro Streaksupporting

confidence: 88%

“…GSE54985). 1 To whom correspondence may be addressed. E-mail: liuz11@janelia.hhmi.org or tjianr@ hhmi.org.…”

Section: Significancementioning

confidence: 99%

“…During early mouse gastrulation, Brachyury (T), a classical enhancer-binding transcription factor (TF), has been reported to be required for the proper development of primitive streak, allantois, axial, and posterior mesoderm (reviewed in ref. 1).…”

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confidence: 99%

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Charting Brachyury-mediated developmental pathways during early mouse embryogenesis

Lolas

Valenzuela

Tjian

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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To gain insights into coordinated lineage-specification and morphogenetic processes during early embryogenesis, here we report a systematic identification of transcriptional programs mediated by a key developmental regulator-Brachyury. High-resolution chromosomal localization mapping of Brachyury by ChIP sequencing and ChIP-exonuclease revealed distinct sequence signatures enriched in Brachyury-bound enhancers. A combination of genomewide in vitro and in vivo perturbation analysis and cross-species evolutionary comparison unveiled a detailed Brachyury-dependent gene-regulatory network that directly links the function of Brachyury to diverse developmental pathways and cellular housekeeping programs. We also show that Brachyury functions primarily as a transcriptional activator genome-wide and that an unexpected gene-regulatory feedback loop consisting of Brachyury, Foxa2, and Sox17 directs proper stem-cell lineage commitment during streak formation. Target gene and mRNA-sequencing correlation analysis of the T c mouse model supports a crucial role of Brachyury in up-regulating multiple key hematopoietic and musclefate regulators. Our results thus chart a comprehensive map of the Brachyury-mediated gene-regulatory network and how it influences in vivo developmental homeostasis and coordination.primitive streak | early development | mesoendoderm differentiation I n the past decade, significant insights have been gained in understanding gene-regulatory programs responsible for embryonic stem (ES) cell pluripotency and self-renewal. However, transcriptional control mechanisms underlying finely balanced lineage-segregation and morphogenetic processes during early mammalian embryogenesis remained elusive. During early mouse gastrulation, Brachyury (T), a classical enhancer-binding transcription factor (TF), has been reported to be required for the proper development of primitive streak, allantois, axial, and posterior mesoderm (reviewed in ref. 1).Specifically, mouse embryos that are homozygous for the Brachyury (T) deletion die at midgestation (2). T −/− mutant epiblast cells are compromised in their ability to migrate away from the primitive streak and, therefore, are unable to undergo the morphogenetic movements carried out by their wild-type (WT) counterparts during gastrulation. In addition to defects in the primitive streak, the notochord is absent in posterior portions of the embryo. Although the anterior portions of T mutant mice contain notochordal precursor-like cells, they fail to undergo normal terminal differentiation (3, 4). The embryonic pattern posterior to the forelimb region of T −/− animals is also disturbed, with somites posterior to the seventh pair absent or abnormal. Although neural folds fuse to form the neural tube, they are severely kinked in the caudal region, and the surface ectoderm tends to form fluid-filled blisters (2, 4, 5). In addition to these well-documented defects, numerous other phenotypic abnormalities have been reported in T −/− and T mutant embryos, including left-right pattern...

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Section: Brachyury Coordinates Gene Expression During In Vitro Streaksupporting

confidence: 88%

“…GSE54985). 1 To whom correspondence may be addressed. E-mail: liuz11@janelia.hhmi.org or tjianr@ hhmi.org.…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Charting Brachyury-mediated developmental pathways during early mouse embryogenesis

Lolas

Valenzuela

Tjian

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Tbx15 is a member of a phylogenetically conserved family of 18 genes, which share a characteristic sequence similarity within the DNA-binding domain (T domain) and are involved in the control of a variety of developmental processes, including mesoderm specification (13,14). In rodents, Tbx15 shows a dorsoventral pattern that mirrors the distribution of the agouti protein (15).…”

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confidence: 99%

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Gesta

Bézy²,

Mori³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Increased intraabdominal (visceral) fat is associated with a high risk of diabetes and metabolic syndrome. We have previously shown that the mesodermal developmental transcription factor Tbx15 is highly differentially expressed between visceral and subcutaneous (s.c.) fat in both humans and rodents, and in humans visceral fat Tbx15 expression is decreased in obesity. Here we show that, in mice, Tbx15 is 260-fold more highly expressed in s.c. preadipocytes than in epididymal preadipocytes. Overexpression of Tbx15 in 3T3-L1 preadipocytes impairs adipocyte differentiation and decreases triglyceride content. This defect in differentiation can be corrected by stimulating cells with the PPARγ agonist rosiglitazone (Rosi). However, triglyceride accumulation remains decreased by ∼50%, due to a decrease in basal lipogenic rate and increase in basal lipolytic rate. 3T3-L1 preadipocytes overexpressing Tbx15 also have a 15% reduction in mitochondrial mass and a 28% reduction in basal mitochondrial respiration (P = 0.004) and ATP turnover (P = 0.02), and a 45% (P = 0.003) reduction in mitochondrial respiratory capacity. Thus, differential expression of Tbx15 between fat depots plays an important role in the interdepot differences in adipocyte differentiation, triglyceride accumulation, and mitochondrial function that may contribute to the risk of diabetes and metabolic disease.thiazolidinedione | bioenergetics profile | Oil Red O

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“…The T-box family of transcription factors has been identified in invertebrates and chordates and is reported to play a crucial role in embryonic development (Kavka and Green, 1997;Papaioannou and Silver, 1998;Smith, 1999;Wilson and Conlon, 2002;Showell et al, 2004). A member of this family, tbx6, is expressed in primitive streaks, paraxial mesoderms, muscle-lineage blastomeres, and tailbuds in various species (Chapman et al, 1996;Yasuo et al, 1996;Hug et al, 1997;Griffin et al, 1998;Uchiyama et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

pMesogenin1 and 2 function directly downstream of Xtbx6 in Xenopus somitogenesis and myogenesis

Tazumi

Yabe

Yokoyama

et al. 2008

Developmental Dynamics

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T-box transcription factor tbx6 and basic-helix-loop-helix transcription factor pMesogenin1 are reported to be involved in paraxial mesodermal differentiation. To clarify the relationship between these genes in Xenopus laevis, we isolated pMesogenin2, which showed high homology with pMesogenin1. Both pMesogenin1 and 2 appeared to be transcriptional activators and were induced by a hormone-inducible version of Xtbx6 without secondary protein synthesis in animal cap assays. The pMesogenin2 promoter contained three potential T-box binding sites with which Xtbx6 protein was shown to interact, and a reporter gene construct containing these sites was activated by Xtbx6. Xtbx6 knockdown reduced pMesogenin1 and 2 expressions, but not vice versa. Xtbx6 and pMesogenin1 and 2 knockdowns caused similar phenotypic abnormalities including somite malformation and ventral body wall muscle hypoplasia, suggesting that Xtbx6 is a direct regulator of pMesogenin1 and 2, which are both involved in somitogenesis and myogenesis including that of body wall muscle in Xenopus laevis. Developmental Dynamics 237: 3749 -3761, 2008.

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T‐box genes in early embryogenesis

Cited by 271 publications

References 144 publications

Charting Brachyury-mediated developmental pathways during early mouse embryogenesis

Charting Brachyury-mediated developmental pathways during early mouse embryogenesis

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

pMesogenin1 and 2 function directly downstream of Xtbx6 in Xenopus somitogenesis and myogenesis

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