Pitx2 regulates cardiac left–right asymmetry by patterning second cardiac lineage-derived myocardium

Ai, Di; Liu, Wei; Ma, Lijiang; Dong, Feiyan; Lu, Mingxia; Wang, Degang; Verzi, Michael P.; Cai, Chen-Leng; Gage, Philip J.; Evans, Sylvia M.; Black, Brian L.; Brown, Nigel A.; Martin, James F.

doi:10.1016/j.ydbio.2006.06.009

Cited by 113 publications

(108 citation statements)

References 55 publications

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“…These Pitx2 ϩ /myogenin Ϫ cells may be either surface ectoderm or neural crest derivatives. Pitx2 expression in neural crest derivatives has also been observed in other regions of the head (20)(21)(22)(23). Pitx2 expression was generally not observed in nonmyogenic territories surrounding anlagen in other regions of the body (17) Severe losses in myogenin ϩ /Pitx2 ϩ territories were observed in the region adjacent to the tongue that represents the vestigial jaw ( Fig.…”

Section: Pitx2 Is Required For Initiation Of Myogenic Progression In mentioning

confidence: 90%

Cranial muscle defects of Pitx2 mutants result from specification defects in the first branchial arch

Shih

Groß

Kioussi³

2007

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

117

143

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Pitx2 expression is observed during all states of the myogenic progression in embryonic muscle anlagen and persists in adult muscle. Pitx2 mutant mice form all but a few muscle anlagen. Loss or degeneration in muscle anlagen could generally be attributed to the loss of a muscle attachment site induced by some other aspect of the Pitx2 phenotype. Muscles derived from the first branchial arch were absent, whereas muscles derived from the second branchial arch were merely distorted in Pitx2 mutants at midgestation. Pitx2 was expressed well before, and was required for, initiation of the myogenic progression in the first, but not second, branchial arch mesoderm. Pitx2 was also required for expression of premyoblast specification markers Tbx1, Tcf21, and Msc in the first, but not second, branchial arch. First, but not second, arch mesoderm of Pitx2 mutants failed to enlarge after embryonic day 9.5, well before the onset of the myogenic progression. Thus, Pitx2 contributes to specification of first, but not second, arch mesoderm. The jaw of Pitx2 mutants was vestigial by midgestation, but significant size reductions were observed as early as embryonic day 10.5. The diminutive first branchial arch of mutants could not be explained by loss of mesoderm alone, suggesting that Pitx2 contributes to the earliest specification of jaw itself.homeobox gene ͉ muscle development

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Section: Pitx2 Is Required For Initiation Of Myogenic Progression In mentioning

confidence: 90%

Cranial muscle defects of Pitx2 mutants result from specification defects in the first branchial arch

Shih

Groß

Kioussi³

2007

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

117

143

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“…We determined that direction of heart looping is specified at approximately the seven-somite stage in the chick (Linask et al, 2005a) and suggested that the asymmetry of cell proliferation and flectin in the anterior heart field may relate to asymmetric patterning of Pitx2c (Ai et al, 2006). The laterality gene Nodal in all vertebrates analyzed shows a left expression in the embryo and heart fields and is upstream of Pitx2c.…”

Section: Reduced Asymmetric Nodal Activity Leads To Abnormal Looping mentioning

confidence: 96%

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

Lu¹,

Seeholzer²,

Han³

et al. 2008

Developmental Dynamics

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Flectin, a protein previously described to be expressed in a left-dominant manner in the embryonic chick heart during looping, is a member of the nonmuscle myosin II (NMHC-II) protein class. During looping, both NMHC-IIA and NMHC-IIB are expressed in the mouse heart on embryonic day 9.5. The patterns of localization of NMHC-IIB, rather than NMHC-IIA in the mouse looping heart and in neural crest cells, are equivalent to what we reported previously for flectin. Expression of full-length human NMHC-IIA and -IIB in 10 T1/2 cells demonstrated that flectin antibody recognizes both isoforms. Electron microscopy revealed that flectin antibody localizes in short cardiomyocyte cell processes extending from the basal layer of the cardiomyocytes into the cardiac jelly. Flectin antibody also recognizes stress fibrils in the cardiac jelly in the mouse and chick heart; while NMHC-IIB antibody does not. Abnormally looping hearts of the Nodal ⌬ 600 homozygous mouse embryos show decreased NMHC-IIB expression on both the mRNA and protein levels. These results document the characterization of flectin and extend the importance of NMHC-II and the cytoskeletal actomyosin complex to the mammalian heart and cardiac looping. Developmental Dynamics 237:3577-3590, 2008.

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“…The bicoid type homeobox gene pitx2 is expressed in the left side of several organ primordia and has an instructive role in mediating left-right organ asymmetries (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). During female chick gonad development, pitx2c mRNA transcripts are restricted to the presumptive left gonad cortex epithelia at stage 14 HH (Fig.…”

Section: Subcellular Asymmetries Of the Left Versus Right Female Chicmentioning

confidence: 99%

“…Unlike other asymmetric genes, pitx2 expression is maintained during the development of several organ primordia, making it a good candidate to be involved in both mediating the maintenance of left-right information from the lateral plate mesoderm to its derived developing organs and executing it at a cellular level. Indeed, Pitx2 loss-and gain-of-function experiments can cause organ-specific laterality defects in all vertebrates analyzed to date (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21).Notwithstanding these advances, we are still far away from understanding how organ primordia interpret left-right genetic information during organogenesis, i.e., how broad domains of side-specific gene expression in the lateral plate mesoderm translate to asymmetric organ development. Moreover, our knowledge on how asymmetric gene activity is linked to specific cellular processes is also still scarce.…”

mentioning

confidence: 99%

Pitx2 regulates gonad morphogenesis

Rodríguez-León

Esteban

Martí

et al. 2008

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

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Organ shape and size, and, ultimately, organ function, relate in part to the cell and tissue spatial arrangement that takes place during embryonic development. Despite great advances in the genetic regulatory networks responsible for tissue and organ development, it is not yet clearly understood how specific gene functions are linked to the specific morphogenetic processes underlying the internal organ asymmetries found in vertebrate animals. During female chick embryogenesis, and in contrast to males where both testes develop symmetrically, asymmetrical gonad morphogenesis results in only one functional ovary. The disposition of paired organs along the left-right body axis has been shown to be regulated by the activity of the homeobox containing gene pitx2. We have found that pitx2 regulates cell adhesion, affinity, and cell recognition events in the developing gonad primordium epithelia. This in turn not only allows for proper somatic development of the gonad cortex but also permits the proliferation and differentiation of primordial germ cells. We illustrate how Pitx2 activity directs asymmetrical gonad morphogenesis by controlling mitotic spindle orientation of the developing gonad cortex and how, by modulating cyclinD1 expression during asymmetric ovarian development, Pitx2 appears to control gonad organ size. All together our observations indicate that the effects elicited by Pitx2 during the development of the female chick ovary are critical for cell topology, growth, fate, and ultimately organ morphogenesis and function.cyclin D1 ͉ left-right asymmetry ͉ chick ovary development ͉ mitotic orientation ͉ primordial germ cell D espite the initial bilateral symmetry of the vertebrate body plan, internal organs, such as the heart, stomach, and intestines, all have a characteristic asymmetric structure and are asymmetrically positioned in the body cavity. The acquisition of proper left-right asymmetries is achieved in a highly conserved manner during embryo development. Since the seminal work more than a decade ago that identified a functional link between asymmetrical gene expression and organ asymmetry (1), our understanding of the molecular and cellular events involved in the establishment of left-right asymmetry in vertebrates has increased enormously. This is indeed the case in the initial establishment of left-right asymmetrical differences that occur during gastrulation as well as during the immediately subsequent stages of embryo development when the local asymmetrical cues in and around the node are deployed to broader domains of gene expression in the lateral plate mesoderm. Once side-specific gene expression domains are established and stabilized in the lateral plate mesoderm, left-right information is transferred to the organ primordial, where left and right side-specific morphogenetic programs are executed (reviewed in refs. 2-6).The identification of several genes that display side-specific patterns of expression within the developing organs has provided an entry point for understanding the molecu...

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Pitx2 regulates cardiac left–right asymmetry by patterning second cardiac lineage-derived myocardium

Cited by 113 publications

References 55 publications

Cranial muscle defects of Pitx2 mutants result from specification defects in the first branchial arch

Cranial muscle defects of Pitx2 mutants result from specification defects in the first branchial arch

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

Pitx2 regulates gonad morphogenesis

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