Limits...
Biphasic Hoxd gene expression in shark paired fins reveals an ancient origin of the distal limb domain.

Freitas R, Zhang G, Cohn MJ - PLoS ONE (2007)

Bottom Line: Studies of zebrafish fins showed that the second phase of Hox expression does not occur, leading to the idea that the origin of digits was driven by addition of the distal Hox expression domain in the earliest tetrapods.The results indicate that a second, distal phase of Hoxd gene expression is not uniquely associated with tetrapod digit development, but is more likely a plesiomorphic condition present the common ancestor of chondrichthyans and osteichthyans.We propose that a temporal extension, rather than de novo activation, of Hoxd expression in the distal part of the fin may have led to the evolution of digits.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Cancer/Genetics Research Complex, University of Florida, Gainesville, Florida, United Sates of America.

ABSTRACT
The evolutionary transition of fins to limbs involved development of a new suite of distal skeletal structures, the digits. During tetrapod limb development, genes at the 5' end of the HoxD cluster are expressed in two spatiotemporally distinct phases. In the first phase, Hoxd9-13 are activated sequentially and form nested domains along the anteroposterior axis of the limb. This initial phase patterns the limb from its proximal limit to the middle of the forearm. Later in development, a second wave of transcription results in 5' HoxD gene expression along the distal end of the limb bud, which regulates formation of digits. Studies of zebrafish fins showed that the second phase of Hox expression does not occur, leading to the idea that the origin of digits was driven by addition of the distal Hox expression domain in the earliest tetrapods. Here we test this hypothesis by investigating Hoxd gene expression during paired fin development in the shark Scyliorhinus canicula, a member of the most basal lineage of jawed vertebrates. We report that at early stages, 5'Hoxd genes are expressed in anteroposteriorly nested patterns, consistent with the initial wave of Hoxd transcription in teleost and tetrapod paired appendages. Unexpectedly, a second phase of expression occurs at later stages of shark fin development, in which Hoxd12 and Hoxd13 are re-expressed along the distal margin of the fin buds. This second phase is similar to that observed in tetrapod limbs. The results indicate that a second, distal phase of Hoxd gene expression is not uniquely associated with tetrapod digit development, but is more likely a plesiomorphic condition present the common ancestor of chondrichthyans and osteichthyans. We propose that a temporal extension, rather than de novo activation, of Hoxd expression in the distal part of the fin may have led to the evolution of digits.

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Model for the origin of digits by temporal extension of distal Hoxd13 expression.Tree shows phylogenetic relationships of shark, paddlefish, zebrafish and mouse. Top row shows hypothetical timing for the transition of the apical ectodermal ridge (AER) to apical ectodermal fold (AEF); note that the mouse maintains an AER and does not form an AEF. Green shading represents proliferative period for endoskeletal progenitor cells. Middle rows show Hoxd13 expression domains (blue) at early and late stages of fin and limb bud outgrowth. AER and AEF are shaded orange. Bottom row shows pectoral appendicular skeleton for each taxon. Endoskeletal bones are shaded as follows: green, propterygium; red, mesopterygium, yellow, metapterygium. Dermal fin rays are shown as unshaded elements within fin blade. The model suggests that a second phase of distal Hoxd13 expression was present in the paired fins of the common ancestor of chondrichthyans and osteichthyans (at position 1), and that loss of the distal Hoxd13 domain in teleosts (position 2) and its spatial expansion in tetrapods (position 3) may have been associated with temporal modulation of endoskeletal progenitor cell proliferation. Early conversion of the AER to an AEF would be expected to truncate or eliminate phase II expression of Hoxd13 and reduce the fin endoskeleton, as seen in zebrafish, whereas prolonged signaling by the AER would be expected to extend Phase II and expand the Hoxd13 domain, giving rise to digits in the tetrapod lineage. Clock model after [25]; skeletal patterns after [15], [31], [40], [74].
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pone-0000754-g005: Model for the origin of digits by temporal extension of distal Hoxd13 expression.Tree shows phylogenetic relationships of shark, paddlefish, zebrafish and mouse. Top row shows hypothetical timing for the transition of the apical ectodermal ridge (AER) to apical ectodermal fold (AEF); note that the mouse maintains an AER and does not form an AEF. Green shading represents proliferative period for endoskeletal progenitor cells. Middle rows show Hoxd13 expression domains (blue) at early and late stages of fin and limb bud outgrowth. AER and AEF are shaded orange. Bottom row shows pectoral appendicular skeleton for each taxon. Endoskeletal bones are shaded as follows: green, propterygium; red, mesopterygium, yellow, metapterygium. Dermal fin rays are shown as unshaded elements within fin blade. The model suggests that a second phase of distal Hoxd13 expression was present in the paired fins of the common ancestor of chondrichthyans and osteichthyans (at position 1), and that loss of the distal Hoxd13 domain in teleosts (position 2) and its spatial expansion in tetrapods (position 3) may have been associated with temporal modulation of endoskeletal progenitor cell proliferation. Early conversion of the AER to an AEF would be expected to truncate or eliminate phase II expression of Hoxd13 and reduce the fin endoskeleton, as seen in zebrafish, whereas prolonged signaling by the AER would be expected to extend Phase II and expand the Hoxd13 domain, giving rise to digits in the tetrapod lineage. Clock model after [25]; skeletal patterns after [15], [31], [40], [74].

Mentions: What, then, do these data tell us about the origin of digits? Firstly, the discovery that the second wave of Hoxd gene expression at the distal tip of paired appendages can be extended to the chondrichthyan lineage allows us to exclude the hypothesis that a novel domain of distal Hoxd expression first appeared in stem-group tetrapods. Secondly, distal Hoxd expression does not itself lead to development of an autopod. The third point relates to the demonstration by Duboule and co-workers that 5′ HoxD and HoxA genes are required for proliferation of skeletogenic precursors cells in the limb [32], [76]. The distal Hoxd domain in shark fins may regulate cell proliferation beneath the AER. As such, its presence at late stages of shark fin and tetrapod limb development, and its absence from zebrafish, would fit with elaboration of the distal skeleton in the former and its truncation in the latter. It is therefore intriguing that the size of the distal expression domain in sharks is extremely narrow relative to that of tetrapods. The pivotal event with respect to the origin of digits may have been a temporal extension of the second transcriptional wave, which would have led to a sustained period of cell proliferation, thereby increasing the size of the distal Hoxd domain, at the terminus of the limb (Fig. 5).


Biphasic Hoxd gene expression in shark paired fins reveals an ancient origin of the distal limb domain.

Freitas R, Zhang G, Cohn MJ - PLoS ONE (2007)

Model for the origin of digits by temporal extension of distal Hoxd13 expression.Tree shows phylogenetic relationships of shark, paddlefish, zebrafish and mouse. Top row shows hypothetical timing for the transition of the apical ectodermal ridge (AER) to apical ectodermal fold (AEF); note that the mouse maintains an AER and does not form an AEF. Green shading represents proliferative period for endoskeletal progenitor cells. Middle rows show Hoxd13 expression domains (blue) at early and late stages of fin and limb bud outgrowth. AER and AEF are shaded orange. Bottom row shows pectoral appendicular skeleton for each taxon. Endoskeletal bones are shaded as follows: green, propterygium; red, mesopterygium, yellow, metapterygium. Dermal fin rays are shown as unshaded elements within fin blade. The model suggests that a second phase of distal Hoxd13 expression was present in the paired fins of the common ancestor of chondrichthyans and osteichthyans (at position 1), and that loss of the distal Hoxd13 domain in teleosts (position 2) and its spatial expansion in tetrapods (position 3) may have been associated with temporal modulation of endoskeletal progenitor cell proliferation. Early conversion of the AER to an AEF would be expected to truncate or eliminate phase II expression of Hoxd13 and reduce the fin endoskeleton, as seen in zebrafish, whereas prolonged signaling by the AER would be expected to extend Phase II and expand the Hoxd13 domain, giving rise to digits in the tetrapod lineage. Clock model after [25]; skeletal patterns after [15], [31], [40], [74].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1937022&req=5

pone-0000754-g005: Model for the origin of digits by temporal extension of distal Hoxd13 expression.Tree shows phylogenetic relationships of shark, paddlefish, zebrafish and mouse. Top row shows hypothetical timing for the transition of the apical ectodermal ridge (AER) to apical ectodermal fold (AEF); note that the mouse maintains an AER and does not form an AEF. Green shading represents proliferative period for endoskeletal progenitor cells. Middle rows show Hoxd13 expression domains (blue) at early and late stages of fin and limb bud outgrowth. AER and AEF are shaded orange. Bottom row shows pectoral appendicular skeleton for each taxon. Endoskeletal bones are shaded as follows: green, propterygium; red, mesopterygium, yellow, metapterygium. Dermal fin rays are shown as unshaded elements within fin blade. The model suggests that a second phase of distal Hoxd13 expression was present in the paired fins of the common ancestor of chondrichthyans and osteichthyans (at position 1), and that loss of the distal Hoxd13 domain in teleosts (position 2) and its spatial expansion in tetrapods (position 3) may have been associated with temporal modulation of endoskeletal progenitor cell proliferation. Early conversion of the AER to an AEF would be expected to truncate or eliminate phase II expression of Hoxd13 and reduce the fin endoskeleton, as seen in zebrafish, whereas prolonged signaling by the AER would be expected to extend Phase II and expand the Hoxd13 domain, giving rise to digits in the tetrapod lineage. Clock model after [25]; skeletal patterns after [15], [31], [40], [74].
Mentions: What, then, do these data tell us about the origin of digits? Firstly, the discovery that the second wave of Hoxd gene expression at the distal tip of paired appendages can be extended to the chondrichthyan lineage allows us to exclude the hypothesis that a novel domain of distal Hoxd expression first appeared in stem-group tetrapods. Secondly, distal Hoxd expression does not itself lead to development of an autopod. The third point relates to the demonstration by Duboule and co-workers that 5′ HoxD and HoxA genes are required for proliferation of skeletogenic precursors cells in the limb [32], [76]. The distal Hoxd domain in shark fins may regulate cell proliferation beneath the AER. As such, its presence at late stages of shark fin and tetrapod limb development, and its absence from zebrafish, would fit with elaboration of the distal skeleton in the former and its truncation in the latter. It is therefore intriguing that the size of the distal expression domain in sharks is extremely narrow relative to that of tetrapods. The pivotal event with respect to the origin of digits may have been a temporal extension of the second transcriptional wave, which would have led to a sustained period of cell proliferation, thereby increasing the size of the distal Hoxd domain, at the terminus of the limb (Fig. 5).

Bottom Line: Studies of zebrafish fins showed that the second phase of Hox expression does not occur, leading to the idea that the origin of digits was driven by addition of the distal Hox expression domain in the earliest tetrapods.The results indicate that a second, distal phase of Hoxd gene expression is not uniquely associated with tetrapod digit development, but is more likely a plesiomorphic condition present the common ancestor of chondrichthyans and osteichthyans.We propose that a temporal extension, rather than de novo activation, of Hoxd expression in the distal part of the fin may have led to the evolution of digits.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Cancer/Genetics Research Complex, University of Florida, Gainesville, Florida, United Sates of America.

ABSTRACT
The evolutionary transition of fins to limbs involved development of a new suite of distal skeletal structures, the digits. During tetrapod limb development, genes at the 5' end of the HoxD cluster are expressed in two spatiotemporally distinct phases. In the first phase, Hoxd9-13 are activated sequentially and form nested domains along the anteroposterior axis of the limb. This initial phase patterns the limb from its proximal limit to the middle of the forearm. Later in development, a second wave of transcription results in 5' HoxD gene expression along the distal end of the limb bud, which regulates formation of digits. Studies of zebrafish fins showed that the second phase of Hox expression does not occur, leading to the idea that the origin of digits was driven by addition of the distal Hox expression domain in the earliest tetrapods. Here we test this hypothesis by investigating Hoxd gene expression during paired fin development in the shark Scyliorhinus canicula, a member of the most basal lineage of jawed vertebrates. We report that at early stages, 5'Hoxd genes are expressed in anteroposteriorly nested patterns, consistent with the initial wave of Hoxd transcription in teleost and tetrapod paired appendages. Unexpectedly, a second phase of expression occurs at later stages of shark fin development, in which Hoxd12 and Hoxd13 are re-expressed along the distal margin of the fin buds. This second phase is similar to that observed in tetrapod limbs. The results indicate that a second, distal phase of Hoxd gene expression is not uniquely associated with tetrapod digit development, but is more likely a plesiomorphic condition present the common ancestor of chondrichthyans and osteichthyans. We propose that a temporal extension, rather than de novo activation, of Hoxd expression in the distal part of the fin may have led to the evolution of digits.

Show MeSH
Related in: MedlinePlus