Patterning Systems—From One End of the Limb to the Other

Tickle, Cheryll

doi:10.1016/s1534-5807(03)00095-9

Cited by 209 publications

(171 citation statements)

References 68 publications

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“…Rather, BMP signaling is required for initial chondrogenesis as outlined above and BMP/pSmad signaling appears to be the driving force for the outgrowth of the digit condensations by means of distally directed chondrogenesis. Montero et al (2008) furthermore showed that the integrity of the DC/ PFR required AER signaling, which links the DC/PFR to the elongation model proposed by Sanz-Ezquerro and Tickle (2003). These studies altogether suggest that the outgrowth of digit condensations depends on a timely and spatially defined input of strong BMP/Smad1/5/8 signaling.…”

Section: Developmental Dynamicsmentioning

confidence: 59%

“…Outgrowth of the limb bud is under the control of fibroblast growth factor (Fgf) signaling from the apical ectodermal ridge (AER), a thickened ectodermal structure that runs along the dorsoventral border of the limb bud (Niswander et al, 1993;Sun et al, 2002). Besides the AER, other signaling centers such as the zone of polarizing activity (ZPA) in the posterior mesenchyme and the dorsal ectoderm specify the three spatial axes of the limb bud (reviewed in Tickle, 2003Tickle, , 2006. These patterning mechanisms in the end generate a morphogenetic field that conveys the information for patterning the skeletal elements as well as other structures in the limb (see e.g., Zeller et al, 2009).…”

Section: Overviewmentioning

confidence: 99%

“…Moreover, it is thought that the interdigital mesenchyme memorizes positional information through local BMP signaling (Dahn and Fallon, 2000;Drossopoulou et al, 2000). Studies performed in the chicken have shown that the number of phalanges in a digit is determined by the duration of AER/Fgf signaling (Sanz-Ezquerro and Tickle, 2003). Prolonged AER signaling led to the development of additional phalanges while precocious ablation of the AER caused a cease of further growth resulting in loss of phalanges.…”

Section: Elongation Of the Initial Condensation By Distally Directed mentioning

confidence: 99%

“…AER ablation results in apoptosis in the underlying mesoderm (Rowe et al, 1982). Chemical inhibition of Fgf signaling during the phase of digit elongation caused the premature termination of outgrowth by induction of the formation of a terminal phalanx and hence loss of the penultimate phalanx (Sanz-Ezquerro and Tickle, 2003). It was thus proposed that one function of Fgf signaling is to inhibit the formation of a distal phalanx to sustain digit elongation in coordination with its role in maintaining the distal progenitor pool (Casanova and Sanz-Ezquerro, 2007).…”

Section: Elongation Of the Initial Condensation By Distally Directed mentioning

confidence: 99%

“…In the chicken, the elongation of the digit ray is carried by elongation and segmentation of the penultimate phalanx. It is noteworthy that each digit appears to have its own critical threshold for segmentation, because the length of phalanges in the chicken foot is different from anterior to posterior digits (SanzEzquerro and Tickle, 2003). Segmentation is under negative control of signals from the previous joint, as well as from signals from the AER.…”

Section: Segmentation Of the Digitsmentioning

confidence: 99%

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Mechanisms of digit formation: Human malformation syndromes tell the story

Stricker

Mundlos

2011

Developmental Dynamics

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Identifying the genetic basis of human limb malformation disorders has been instrumental in improving our understanding of limb development. Abnormalities of the hands and/or feet include defects affecting patterning, establishment, elongation, and segmentation of cartilaginous condensations, as well as growth of the individual skeletal elements. While the phenotype of such malformations is highly diverse, the mutations identified to date cluster in genes implicated in a limited number of molecular pathways, namely hedgehog, Wnt, and bone morphogenetic protein. The latter pathway appears to function as a key molecular network regulating different phases of digit and joint development. Studies in animal models not only extended our insight into the pathogenesis of these conditions, but have also contributed to our understanding of the in vivo functions and interactions of these key players. This review is aimed at integrating the current understanding of human digit malformations into the increasing knowledge of the molecular mechanisms of digit development. Developmental Dynamics 240:990-1004,

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Section: Developmental Dynamicsmentioning

confidence: 59%

Section: Overviewmentioning

confidence: 99%

Section: Elongation Of the Initial Condensation By Distally Directed mentioning

confidence: 99%

Section: Elongation Of the Initial Condensation By Distally Directed mentioning

confidence: 99%

Section: Segmentation Of the Digitsmentioning

confidence: 99%

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Mechanisms of digit formation: Human malformation syndromes tell the story

Stricker

Mundlos

2011

Developmental Dynamics

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Evolution of Vertebrate Limb Development

Tanaka¹

2009

Encyclopedia of Life Sciences

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The origin and diversification of fins and limbs have long been a focus of interest to both palaeontologists and developmental biologists. Studies conducted in recent decades have resulted in enormous progress in the understanding of the genetic and developmental bases of the evolution of paired appendages in vertebrates. These discoveries in the areas of genetics and developmental biology have shed light on the mechanisms underlying the evolution of this key morphological innovation in vertebrates. In this article, I discuss recent advances in these fields and how they can provide a mechanistic explanation for the origin and evolution of paired appendages. Key Concepts According to the fossil record, single pair of fin‐like structures emerged in the bodies of certain ancestral jawless vertebrates, and two pairs of fins are unique to jawed vertebrates. There are two separate phases/waves of Hoxd gene expression in tetrapod limbs. The first wave precedes the formation of the proximal parts of the limb, whereas the second wave corresponds to the most distal part of the limb (digits). The earliest known amphibian fossils, Acanthostega and Ichthyostega , seem to have had more than five digits in their limbs. It has been proposed that regulatory changes in Hox and/or Shh expression modified the digit number during evolution. Regulatory modifications of specific gene expression appear to account for the evolution of paired appendages, such as the increasing length of bat wings, the loss of limbs in pythons, and pelvic reduction in sticklebacks.

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The Limbs

Ferretti¹,

Tickle

2008

Embryos, Genes and Birth Defects

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Patterning Systems—From One End of the Limb to the Other

Cited by 209 publications

References 68 publications

Mechanisms of digit formation: Human malformation syndromes tell the story

Mechanisms of digit formation: Human malformation syndromes tell the story

Evolution of Vertebrate Limb Development

The Limbs

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