Distinct WNT Pathways Regulating AER Formation and Dorsoventral Polarity in the Chick Limb Bud

Kengaku, Mineko; Capdevila, Javier; Rodrı́guez-Esteban, Concepción; Peña, J. De La; Johnson, Randy L.; Belmonte, Juan Carlos Izpisúa; Tabin, Clifford J.

doi:10.1126/science.280.5367.1274

Cited by 388 publications

(395 citation statements)

References 36 publications

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“…In Lef1 -/-/Tcf1 -/-double-mutant embryos, Tbx5 expression is unaffected and limb bud outgrowth is initiated, but the AER does not form and outgrowth is not maintained (Galceran et al, 1999). This is consistent with the proposed roles of Wnt3 in the mouse (Barrow et al, 2003) and Wnt3a in the chick (Kengaku et al, 1998;Kengaku et al, 1997) in AER formation.…”

Section: A Genetic Hierarchy In Limb Initiation and Outgrowthsupporting

confidence: 75%

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: A Genetic Hierarchy In Limb Initiation and Outgrowthsupporting

confidence: 75%

Finger or toe: the molecular basis of limb identity

Logan¹

2003

Development

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“…A similar mechanism operates in the vertebrate limb bud to induce and maintain the apical ectodermal ridge (AER). While the AER emits Fgf as a long-range organizing signal, it is initially induced by Wnt3/Wnt3a and requires a coherent front of Delta-Notch signaling (Laufer et al, 1997;Rodriguez-Esteban et al, 1997;Kengaku et al, 1998;Kawakami et al, 2001;Barrow et al, 2003). The similarities between these diverse systems could reflect cooption of a conserved developmental module-a self-reinforcing genetic/signaling feedback loop that spatially organizes large fields of cells.…”

Section: Discussionmentioning

confidence: 99%

Rhombomere boundaries are Wnt signaling centers that regulate metameric patterning in the zebrafish hindbrain

Riley

Chiang

Storch

et al. 2004

Developmental Dynamics

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The vertebrate hindbrain develops from a series of segments (rhombomeres) distributed along the anteroposterior axis. We are studying the roles of Wnt and Delta-Notch signaling in maintaining rhombomere boundaries as organizing centers in the zebrafish hindbrain. Several wnt genes (wnt1, wnt3a, wnt8b, and wnt10b) show elevated expression at rhombomere boundaries, whereas several delta genes (dlA, dlB, and dlD) are expressed in transverse stripes flanking rhombomere boundaries. Partial disruption of Wnt signaling by knockdown of multiple wnt genes, or the Wnt mediator tcf3b, ablates boundaries and associated cell types. Expression of dlA is chaotic, and cell types associated with rhombomere centers are disorganized. Similar patterning defects are observed in segmentation mutants spiel-ohne-grenzen (spg) and valentino (val), which fail to form rhombomere boundaries due to faulty interactions between adjacent rhombomeres. Stripes of wnt expression are variably disrupted, with corresponding disturbances in metameric patterning. Mutations in dlA or mind bomb (mib) disrupt Delta-Notch signaling and cause a wide range of patterning defects in the hindbrain. Stripes of wnt1 are initially normal but subsequently dissipate, and metameric patterning becomes increasingly disorganized. Driving wnt1 expression using a heat-shock construct partially rescues metameric patterning in mib mutants. Thus, rhombomere boundaries act as Wnt signaling centers required for precise metameric patterning, and Delta signals from flanking cells provide feedback to maintain wnt expression at boundaries. Similar feedback mechanisms operate in the Drosophila wing disc and vertebrate limb bud, suggesting coaptation of a conserved signaling module that spatially organizes cells in complex organ systems.

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“…During development, canonical ligand Wnt3a maintains apical ectodermal cells of limb buds in a highly proliferative state and is, thus, essential to embryonic skeletal development 110, 111. Loss‐of‐function mutations of Wnt coreceptor LRP5 cause reduced bone mass, skeletal fragility, and osteoporosis 112.…”

Section: Implication Of Canonical Wnt Signaling In Vcmentioning

confidence: 99%