Loss of Tbx4 blocks hindlimb development and affects vascularization and fusion of the allantois

Naiche, L.A.; Papaioannou, Virginia E.

doi:10.1242/dev.00504

Cited by 220 publications

(217 citation statements)

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“…Normal Fgf signalling in mutant limb mesenchyme may explain why limb bud initiation proceeds normally in Tbx4 null embryos. Pitx1 expression is also maintained in mutant embryos, indicating that its expression is not dependent on Tbx4 (Naiche and Papaioannou, 2003). This may also explain how normal hindlimb initiation occurs in the absence of Tbx4; the loss of Tbx4 in the hindlimbs may be compensated for by a Pitx gene.…”

Section: Tbx4 and Hindlimb Developmentmentioning

confidence: 94%

“…In mouse embryos mutant for Tbx4, hindlimb bud induction and initial patterning occurs normally. However, at later stages of development Fgf10 expression is not maintained in the mesenchyme and mutant limbs fail to develop beyond early limb bud stages (Naiche and Papaioannou, 2003). In addition to displaying hindlimb defects, Tbx4 mutant embryos fail to undergo chorioallantoic fusion.…”

Section: Tbx4 and Hindlimb Developmentmentioning

confidence: 99%

“…In these embryos, at early stages of hindlimb initiation, Fgf8 is expressed normally in the AER. Msx1, a gene normally expressed in the underlying mesenchyme in response to Fgf signalling from the AER, is also unaffected (Naiche and Papaioannou, 2003). The establishment of normal Fgf signalling in mutant limb mesenchyme was confirmed by the distribution of doubly phophorylated Erk protein (dpErk), which detects activation of the Map kinase cascade by the Fgf receptor and serves as a read-out of Fgf signalling.…”

Section: Tbx4 and Hindlimb Developmentmentioning

confidence: 99%

“…Mouse No forelimb (Agarwal et al, 2003; Hindlimb initiated but no limb outgrowth Hindlimb forms but hindlimb characteristics lost (Lanctot Rallis et al, 2003) (Naiche andPapaioannou, 2003) et al, 1999;Szeto et al, 1999;Marcil et al, 2003) Chick No wing (Rallis et al, 2003;Takeuchi et al, No hindlimb (Takeuchi et al, 2003;N/D 2003;Ng et al, 2002) Ng et al, 2002 Zebrafish No pectoral fin (Ng et al, 2002;Ahn et al, N/D N/D 2002;Garrity et al, 2002) N/D = not determined.…”

Section: Tbx5mentioning

confidence: 99%

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Finger or toe: the molecular basis of limb identity

Logan¹

2003

Development

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Despite their obvious similarities, the forelimbs and hindlimbs of tetrapod vertebrates have evolved distinct structural elements to carry out their discrete functions. Many genes required for limb initiation and patterning are involved in regulatory networks common to both limb-types. Other genes are differentially expressed between forelimb and hindlimb, and have been implicated in the initiation of limb bud outgrowth and the specification of limb-type identity. In this review, I will discuss the current understanding of how genes that control limb identity interact with regulatory networks common to both appendages to produce the fingers of the hand and toes of the foot.

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Section: Tbx4 and Hindlimb Developmentmentioning

confidence: 94%

Section: Tbx4 and Hindlimb Developmentmentioning

confidence: 99%

Section: Tbx4 and Hindlimb Developmentmentioning

confidence: 99%

Section: Tbx5mentioning

confidence: 99%

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Finger or toe: the molecular basis of limb identity

Logan¹

2003

Development

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“…Several T-box genes are expressed in the limb (Naiche et al, 2005), and heterozygous mutations in TBX3, TBX4 and TBX5 cause limb defects in humans (Bamshad et al, 1997;Basson et al, 1997;Bongers et al, 2004). In mouse, all of the Tbx2 subfamily (Tbx2, Tbx3, Tbx4 and Tbx5) have been shown to play roles in limb development (Agarwal et al, 2003;Davenport et al, 2003;Harrelson et al, 2004;Naiche and Papaioannou, 2003). Tbx5 is expressed specifically in the forelimb, while Tbx4, a closely related gene, is expressed in the hindlimb.…”

Section: Introductionmentioning

confidence: 99%

Tbx4is not required for hindlimb identity or post-bud hindlimb outgrowth

Naiche

Papaioannou

2007

Development

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Tbx4 is a crucial gene in the initiation of hindlimb development and has been reported as a determinant of hindlimb identity and a presumptive direct regulator of Fgf10 in the limb. Using a conditional allele of Tbx4, we have ablated Tbx4 function before and after limb initiation. Ablation of Tbx4 before expression in the hindlimb field confirms its requirement for limb bud outgrowth. However, ablation of Tbx4 shortly after onset of expression in the hindlimb field, during limb bud formation, alters neither limb outgrowth nor expression of Fgf10. Instead, post-limb-initiation loss of Tbx4 results in reduction of limb core tissue and hypoplasia of proximal skeletal elements. Loss of Tbx4 during later limb outgrowth produces no limb defects, revealing a brief developmental requirement for Tbx4 function. Despite evidence from ectopic expression studies, our work establishes that loss of Tbx4 has no effect on hindlimb identity as assessed by morphology or molecular markers.

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Vertebrate Embryo: Limb Development

Tickle

2016

Encyclopedia of Life Sciences

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Vertebrate limbs develop from small buds of mesenchyme cells encased in ectoderm. Limb development is an excellent model system for studying embryonic growth and pattern formation. Both processes are governed by cell–cell interactions involving signalling centres that operate along each of the three limb axes, but are functionally interconnected. The main proliferative and positional signals are WNTs, FGFs, SHH and BMPs. Considerable progress has been made in identifying molecules that initiate bud formation including the TBX4/5 transcription factors and unravelling the regulatory pathways that establish the signalling centres. Hox genes are involved in multiple steps in establishing the anteroposterior signalling centre in the forelimb. They are also expressed in response to positional signals in the limb buds with a late‐phase controlling digit development. The transcription factor, LMX1B, specifies dorsal development. The transcription factor PITX1 is a major hindlimb determinant but how positional information is interpreted is largely unknown. Key Concepts The limb develops from a bud of mesoderm cells encased in ectoderm which grows out from the body wall. The limb bud mesoderm is made up of cells with two different origins; cells of the lateral plate mesoderm which give rise to the connective tissues and cells that have migrated from the somites which give rise to the myogenic cells of the limb muscles. Three sets of cell–cell interactions specify positional information; one set of interactions operating along each of the three axes of the limb. The apical ectodermal ridge at the tip of the limb bud produces FGFs which are required for bud outgrowth and laying down the proximodistal limb pattern. The dorsal and ventral ectoderm of the limb bud produce WNT7a and BMPs, respectively, which are involved in specifying dorsoventral positional information. The polarising region, a mesodermal signalling region at the posterior margin of the limb bud, produces Sonic Hedgehog (SHH) which specifies anteroposterior positional information and controls growth across this axis. Hox5 and Hox9 paralogous genes of the Hox clusters are involved in establishing the initial anteroposterior polarity of the buds that will develop into forelimbs. Interactions between the signalling regions ensure that pattern formation is integrated along all three axes of the developing limb. 5′ genes in the HoxA and HoxD clusters are expressed in early and late limb buds under the control of long‐range enhancers located, respectively, 3′ and 5′ of the cluster, with the early phase of activity being involved in establishing Shh expression in the polarising region and the later phase development of the digits. The differences between forelimbs and hindlimbs depend on the interpretation of positional information, with the transcription factor PITX1 being a major hindlimb determinant.

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Loss of Tbx4 blocks hindlimb development and affects vascularization and fusion of the allantois

Cited by 220 publications

References 62 publications

Finger or toe: the molecular basis of limb identity

Finger or toe: the molecular basis of limb identity

Tbx4is not required for hindlimb identity or post-bud hindlimb outgrowth

Vertebrate Embryo: Limb Development

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