Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function

Kmita, Marie; Tarchini, Basile; Zákány, József; Logan, Malcolm; Tabin, Clifford J.; Duboule, Denis

doi:10.1038/nature03648

Cited by 239 publications

(242 citation statements)

References 28 publications

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“…Shh is not activated and only a truncated femur is observed in the forelimb at birth together with a piece of unossified presumptive zeugopod, similar to Shh null mutants but less well developed (Kmita et al, 2005). In zebrafish, lack of Hand2 is more drastic in abrogating pectoral fin polarity than lack of Shh (syu; Yelon et al, 2000).…”

Section: Hoxd Genes and Early Posterior Restriction Of The Zpamentioning

confidence: 99%

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

Robert

Lallemand

2006

Developmental Dynamics

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The limb has been a privileged object of investigation and reflection for scientists over the past two centuries and continues to provide a heuristic framework to analyze vertebrate development. Recently, accumulation of new data has significantly changed our view on the mechanisms of limb patterning, in particular along the anterior-posterior axis. These data have led us to revisit the mode of action of the zone of polarizing activity. They shed light on the molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling pathway and give insights into the mechanism of activation of these cardinal factors, as well as the consequences of their activity. These new data are in good part the result of systematic Application of tools used in contemporary mouse molecular genetics. These have extended the power of mouse genetics by introducing mutational strategies that allow fine-tuned modulation of gene expression, interchromosomal deletions and duplication. They have even made the mouse embryo amenable to cell lineage analysis that used to be the realm of chick embryos. In this review, we focus on the data acquired over the last five years from the analysis of mouse limb development and discuss new perspectives opened by these results. Developmental Dynamics 235:2337-2352, 2006.

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Section: Hoxd Genes and Early Posterior Restriction Of The Zpamentioning

confidence: 99%

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

Robert

Lallemand

2006

Developmental Dynamics

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“…This model also agrees with in vitro data according to which Tbx5 alone is capable of driving expression of an Fgf10 reporter (Agarwal et al, 2003;Ng et al, 2002). The differential requirement for T-box genes between initiation and maintenance of FGF signaling also explains the disparity in Tbx4 and Tbx5 conditional phenotypes when combined with the Prx-cre allele, as this transgene has been observed to start expression relatively later in the hindlimb than in the forelimb (Kmita et al, 2005;Logan et al, 2002), and does not seem to ablate Tbx4 gene function until after an FGF feedback loop has formed.…”

Section: A Model For Tbx4 and Tbx5 Function In The Limbmentioning

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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“…Recent work has revealed the reiterated functions of essential regulatory genes, such as Hox genes in appendage development (Table 1; Zakany et al, 2004;Kmita et al, 2005). Furthermore, genetic interactions between such genes may differ depending on the developmental context in early limb bud and late stage limb formation (Zakany et al, 2004).…”

Section: Reiterated Involvement Of Regulatory Genes For Appendage Devmentioning

confidence: 99%

Molecular genetic cascades for external genitalia formation: An emerging organogenesis program

Yamada

Suzuki

Haraguchi

et al. 2006

Developmental Dynamics

109

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Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function

Cited by 239 publications

References 28 publications

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

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

Molecular genetic cascades for external genitalia formation: An emerging organogenesis program

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