A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis

Guo, Caiwei; Sun, Ye; Zhou, Bin; Adam, Rosalyn M.; Li, Xiao Kun; Pu, William T.; Morrow, Bernice E.; Moon, Anne; Li, Xue

doi:10.1172/jci58358

Cited by 25 publications

(38 citation statements)

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“…The expression levels of both Fgf8, which is genetically linked to Tbx1 in the context of DGS (35), and Bmp4, which was shown to act downstream of Lhx2 during eye development (36), were comparable in Lhx2 mutant and control embryos (Fig. S7 A-D).…”

Section: ;Lhx2mentioning

confidence: 93%

Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis

Harel

Maezawa

Avraham

et al. 2012

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

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The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/ velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.

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Section: ;Lhx2mentioning

confidence: 93%

Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis

Harel

Maezawa

Avraham

et al. 2012

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

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“…Indeed, there is a significant coincidence of thyroid dysgenesis and cardiovascular malformations in humans (Devos et al, 1999), indicating that normal development of the thyroid and heart are in some way linked. The fact that both processes are influenced by transcription factors such as Nkx2-5 (Searcy et al, 1998;Dentice et al, 2006), Isl1 (Cai et al, 2003;Westerlund et al, 2008) and Tbx1 (Fagman et al, 2007;Guo et al, 2011) in mice further supports the possibility of shared developmental traits. It should be noted that, although important for morphogenesis, embryonic vessels do not have an inductive role for the thyroid, as shown in the zebrafish cloche mutant which is devoid of any vascularization .…”

Section: Extrinsic Factors That Regulate Thyroid Morphogenesismentioning

confidence: 96%

Development of the thyroid gland

2017

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Thyroid hormones are crucial for organismal development and homeostasis. In humans, untreated congenital hypothyroidism due to thyroid agenesis inevitably leads to cretinism, which comprises irreversible brain dysfunction and dwarfism. Elucidating how the thyroid gland -the only source of thyroid hormones in the bodydevelops is thus key for understanding and treating thyroid dysgenesis, and for generating thyroid cells in vitro that might be used for cell-based therapies. Here, we review the principal mechanisms involved in thyroid organogenesis and functional differentiation, highlighting how the thyroid forerunner evolved from the endostyle in protochordates to the endocrine gland found in vertebrates. New findings on the specification and fate decisions of thyroid progenitors, and the morphogenesis of precursor cells into hormone-producing follicular units, are also discussed.

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“…Previous animal researches had reported that Eya1-null mice exhibited cleft secondary palate or abnormally fused palatal shelves with the nasal septum (24). SIX1/EYA1 compound mutant mice manifested, in addition to cardiovascular defects, a spectrum of craniofacial phenotypes including micrognathia (small jaw) and cleft palate (21). In the same study, researchers found that TBX1 was a genetic upstream regulator of SIX1 and EYA1, and the SIX1/EYA1 transcription complex directly controlled FGF8 expression.…”

Section: Discussionmentioning

confidence: 96%

Associations between EYA1 single‐nucleotide polymorphisms and non‐syndromic orofacial clefts in Western Han Chinese

Zeng

Zhu

et al. 2013

J Oral Pathology Medicine

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A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis

Abstract: A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis

Cited by 25 publications

References 0 publications

Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis

Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis

Development of the thyroid gland

Associations between EYA1 single‐nucleotide polymorphisms and non‐syndromic orofacial clefts in Western Han Chinese

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