An intrinsic timer specifies distal structures of the vertebrate limb

Saiz-Lopez, Patricia; Chinnaiya, Kavitha; Campa, Víctor M.; Delgado, Irene; Ros, María A.; Towers, Matthew

doi:10.1038/ncomms9108

Cited by 51 publications

(109 citation statements)

References 31 publications

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“…In the chick wing bud, Hoxa13 expression is initiated at HH22 in an intrinsically timed manner and continues to be expressed through development, at least until day 10 (Saiz- Lopez et al, 2015). In our experiments, either grafts of HH24, HH27, or two serial grafts of HH24 GFP-expressing distal cells maintained expression of Hoxa13 when grafted under the AER of HH20 host buds (Fig.…”

Section: Resultsmentioning

confidence: 76%

“…Briefly, the procedure consists of grafting 150 µm blocks of distal mesenchyme cells of donor GFP-expressing chick wings denuded of ectoderm under the AER of wild-type host buds. In homochronic grafts, stage HH20 distal cells gave rise to the zeugopod and autopod while HH24 distal cells produce only the entire autopod (Saiz-Lopez et al, 2015; see blue and red asterisks in Fig. 1L).…”

Section: Resultsmentioning

confidence: 99%

“…It is known that cells from different stages and proximo-distal levels of the limb sort out, both in vivo and in culture, and this provides a read-out of positional values Saiz-Lopez et al, 2015;Wada, 2011;Wada and Ide, 1994). It is also known that the product of the Hoxa13 gene is one of the key determinants of this process (Stadler et al, 2001;Yajima et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

“…radius/ulna) and then the autopod (i.e. the digits) (Roselló-Díez et al, 2014;Saiz-Lopez et al, 2015). This intrinsic timer operates in distal limb mesenchyme cells after they have been freed from the influence of proximal signals as a consequence of growth of the bud.…”

Section: Introductionmentioning

confidence: 99%

“…The mechanisms by which limb progenitor cells acquire progressively more distal fates have been subject to intense investigation over many years (Delgado and Torres, 2016). We recently presented a complete model of embryonic proximo-distal (PD) limb development that is composed of two sequential phases (Saiz-Lopez et al, 2015). During the initial phase, signals from the flank of the embryo and from the distal tip of the emerging limb bud specify the structures of the stylopod (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Intrinsic properties of limb bud cells can be differentially reset

et al. 2017

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An intrinsic timing mechanism specifies the positional values of the zeugopod (i.e. radius/ulna) and then autopod (i.e. wrist/digits) segments during limb development. Here, we have addressed whether this timing mechanism ensures that patterning events occur only once by grafting GFP-expressing autopod progenitor cells to the earlier host signalling environment of zeugopod progenitor cells. We show by detecting Hoxa13 expression that early and late autopod progenitors fated for the wrist and phalanges, respectively, both contribute to the entire host autopod, indicating that the autopod positional value is irreversibly determined. We provide evidence that Hoxa13 provides an autopod-specific positional value that correctly allocates cells into the autopod, most likely through the control of cellsurface properties as shown by cell-cell sorting analyses. However, we demonstrate that only the earlier autopod cells can adopt the host proliferation rate to permit normal morphogenesis. Therefore, our findings reveal that the ability of embryonic cells to differentially reset their intrinsic behaviours confers robustness to limb morphogenesis. We speculate that this plasticity could be maintained beyond embryogenesis in limbs with regenerative capacity.

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Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intrinsic properties of limb bud cells can be differentially reset

et al. 2017

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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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Vertebrate Embryo: Limb Development

Tickle

Towers

2020

Encyclopedia of Life Sciences

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An intrinsic timer specifies distal structures of the vertebrate limb

Cited by 51 publications

References 31 publications

Intrinsic properties of limb bud cells can be differentially reset

Intrinsic properties of limb bud cells can be differentially reset

Vertebrate Embryo: Limb Development

Vertebrate Embryo: Limb Development

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