An Additional Limb Can Be Induced from the Flank of the Chick Embryo by FGF4

Ohuchi, Hideyo; Nakagawa, Takashi; Yamauchi, Masaki; Ohata, Takeshi; Yoshioka, Hidefumi; Kuwana, Takashi; Mima, Tatsuya; Matsukawa, Takashi; Nohno, Tsutomu; Noji, Sumihare

doi:10.1006/bbrc.1995.1572

Cited by 102 publications

(51 citation statements)

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“…Recently, however, progress has been made in the induction of spawning in captive animals, which should greatly facilitate the use of amphioxus as an experimental system (28). It will be fascinating to determine whether the ventral mesoderm of amphioxus larvae has any outgrowth potential, and, if so, to investigate the temporal window of this competence, similar to previous experiments, which show that an exogenous source of FGF applied to the chick flank can induce ectopic limb formation (13,14).…”

Section: Discussionmentioning

confidence: 74%

“…First, before duplication of the Tbx4/5 gene, mutations within the coding region endowed the descendant paralogous genes, Tbx5 and Tbx4, with the potential to initiate limb outgrowth; specifically, the proteins acquired the ability to activate Fgf10 in the LPM. Second, that after the divergence of cephalochordates, mutation(s) in the regulatory regions of the ancestral Tbx4/5 locus, led ultimately to the expression of the vertebrate Tbx4 and Tbx5 genes in the early LPM before limb bud stages, when this tissue is competent to initiate limb outgrowth (13,14). To investigate this further, we undertook two complementary approaches: first, we tested the potential of the amphioxus Tbx4/5 protein to initiate limb outgrowth in the forelimbless Tbx5 conditional knockout mouse (10) and second, we tested the ability of the AmphiTbx4/5 and mouse Tbx5 and Tbx4 genomic regions to drive gene expression in the early LPM by transient transgenesis experiments in the mouse.…”

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confidence: 99%

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Tbx4/5 gene duplication and the origin of vertebrate paired appendages

Minguillón

Gibson‐Brown

Logan

2009

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

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Paired fins/limbs are one of the most successful vertebrate innovations, since they are used for numerous fundamental activities, including locomotion, feeding, and breeding. Gene duplication events generate new genes with the potential to acquire novel functions, and two rounds of genome duplication took place during vertebrate evolution. The cephalochordate amphioxus diverged from other chordates before these events and is widely used to deduce the functions of ancestral genes, present in single copy in amphioxus, compared to the functions of their duplicated vertebrate orthologues. The T-box genes Tbx5 and Tbx4 encode two closely related transcription factors that are the earliest factors required to initiate forelimb and hind limb outgrowth, respectively. Since the genetic components proposed to be responsible for acquiring a trait during evolution are likely to be involved in the formation of that same trait in living organisms, we investigated whether the duplication of an ancestral, single Tbx4/5 gene to give rise to distinct Tbx4 and Tbx5 genes has been instrumental in the acquisition of limbs during vertebrate evolution. We analyzed whether the amphioxus Tbx4/5 gene is able to initiate limb outgrowth, and assayed the amphioxus locus for the presence of limb-forming regulatory regions. We show that AmphiTbx4/5 is able to initiate limb outgrowth and, in contrast, that the genomic locus lacks the regulatory modules required for expression that would result in limb formation. We propose that changes at the level of Tbx5 and Tbx4 expression, rather than the generation of novel protein function, have been necessary for the acquisition of paired appendages during vertebrate evolution.S ince Ohno's visionary hypothesis concerning the origin of vertebrate innovations by genome duplication (1), numerous reports have been published supporting this concept (reviewed in ref.2). The cephalochordate amphioxus, a limbless extant invertebrate relative of the vertebrates (3), has been extensively used to study the ancestral functions of genes, present in single copy in amphioxus, that have been duplicated in the vertebrate lineage. Amphioxus exhibits many basal chordate characteristics, including the presence of a dorsal nerve cord, a notochord, and segmented paraxial mesoderm, but lacks many vertebrate characteristics such as migratory neural crest cells, a cranium, or an endoskeleton (4). We sought to investigate the origin of one of the most successful vertebrate innovations, paired appendages, which include the pectoral and pelvic fins of fish and their derived homologues, the forelimbs and hind limbs of tetrapods.The T-box genes Tbx4 and Tbx5 are paralogous genes that arose by duplication of a single, ancestral Tbx4/5 gene. Extant amphioxus possesses a single Tbx4/5 gene (AmphiTbx4/5) (5) and lacks paired appendages, whereas all jawed vertebrates with two pairs of paired appendages have distinct, postduplication Tbx4 and Tbx5 genes. In vertebrates, Tbx5 is expressed in the lateral plate mesoderm (LPM) of the presump...

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Section: Discussionmentioning

confidence: 74%

mentioning

confidence: 99%

Tbx4/5 gene duplication and the origin of vertebrate paired appendages

Minguillón

Gibson‐Brown

Logan

2009

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

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“…Ectopic limbs form following the application of Fgfs to the cells of the interlimb flank of the chick (Cohn et al, 1995;Ohuchi et al, 1995). The type of limb that forms (wing or leg) depends upon the rostrocaudal level at which the Fgf is applied.…”

Section: Lessons From Classical Embryological Studiesmentioning

confidence: 99%

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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“…FGF-2 or FGF-4 will support virtually complete limb outgrowth of limb-buds from which the apical ectodermal ridge had been surgically removed Fallon et al, 1994). The ectopic overexpression of FGF-2 in the anterior chick limb bud results in parallel duplications of skeletal elements (Riley et al, 1993) and the overexpression of FGF-1, FGF-2, or FGF-4 in the flank leads to the formation of extra limbs (Cohn et al, 1995;Ohuchi et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Changes in the expression of fibroblast growth factor receptors mark distinct stages of chondrogenesis in vitro and during chick limb skeletal patterning

Szebenyi

Savage

Olwin

et al. 1995

Developmental Dynamics

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Members of the fibroblast growth factor (FGF) family of growth factors are key regulators of limb skeletal patterning and growth. Abnormal expression of FGFs or mutations in their receptors (fgfrs) result in skeletal disorders. Here we show that changes in the expression of f&s are intrinsic properties of differentiating cartilage. In mesenchymal micromass cultures differentiating into cartilage, as in ovo, fgfr 1 mRNA was found predominantly in undifferentiated, proliferating mesenchyme, f& 2 in precartilage cell aggregates, and fgfi-3 in differentiating cartilage nodules. Thus, our data suggest that switches in the expression of fgfr 1, 2, and 3 mRNAs are associated with phases of cartilage patterning both in vitro and in ovo, and mark distinct stages in the development of the limb skeleton. o 1995 Wiley-Lisa, Inc.

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An Additional Limb Can Be Induced from the Flank of the Chick Embryo by FGF4

Cited by 102 publications

References 0 publications

Tbx4/5 gene duplication and the origin of vertebrate paired appendages

Tbx4/5 gene duplication and the origin of vertebrate paired appendages

Finger or toe: the molecular basis of limb identity

Changes in the expression of fibroblast growth factor receptors mark distinct stages of chondrogenesis in vitro and during chick limb skeletal patterning

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