Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development

Although decades of studies have produced a generalized model for tetrapod limb development, urodeles deviate from anurans and amniotes in at least two key respects: their limbs exhibit preaxial skeletal differentiation and do not develop an apical ectodermal ridge (AER). Here, we investigated how S...

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Main Authors: Sruthi Purushothaman, Ahmed Elewa, Ashley W Seifert
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2019-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/48507
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author Sruthi Purushothaman
Ahmed Elewa
Ashley W Seifert
author_facet Sruthi Purushothaman
Ahmed Elewa
Ashley W Seifert
author_sort Sruthi Purushothaman
collection DOAJ
description Although decades of studies have produced a generalized model for tetrapod limb development, urodeles deviate from anurans and amniotes in at least two key respects: their limbs exhibit preaxial skeletal differentiation and do not develop an apical ectodermal ridge (AER). Here, we investigated how Sonic hedgehog (Shh) and Fibroblast growth factor (Fgf) signaling regulate limb development in the axolotl. We found that Shh-expressing cells contributed to the most posterior digit, and that inhibiting Shh-signaling inhibited Fgf8 expression, anteroposterior patterning, and distal cell proliferation. In addition to lack of a morphological AER, we found that salamander limbs also lack a molecular AER. We found that amniote and anuran AER-specific Fgfs and their cognate receptors were expressed entirely in the mesenchyme. Broad inhibition of Fgf-signaling demonstrated that this pathway regulates cell proliferation across all three limb axes, in contrast to anurans and amniotes where Fgf-signaling regulates cell survival and proximodistal patterning.
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spelling doaj.art-752759c9c24e4d2b8ae2e80e01dfdeb12022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2019-09-01810.7554/eLife.48507Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb developmentSruthi Purushothaman0https://orcid.org/0000-0002-3974-4731Ahmed Elewa1https://orcid.org/0000-0002-1988-7970Ashley W Seifert2https://orcid.org/0000-0001-6576-3664Department of Biology, University of Kentucky, Lexington, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesDepartment of Biology, University of Kentucky, Lexington, United StatesAlthough decades of studies have produced a generalized model for tetrapod limb development, urodeles deviate from anurans and amniotes in at least two key respects: their limbs exhibit preaxial skeletal differentiation and do not develop an apical ectodermal ridge (AER). Here, we investigated how Sonic hedgehog (Shh) and Fibroblast growth factor (Fgf) signaling regulate limb development in the axolotl. We found that Shh-expressing cells contributed to the most posterior digit, and that inhibiting Shh-signaling inhibited Fgf8 expression, anteroposterior patterning, and distal cell proliferation. In addition to lack of a morphological AER, we found that salamander limbs also lack a molecular AER. We found that amniote and anuran AER-specific Fgfs and their cognate receptors were expressed entirely in the mesenchyme. Broad inhibition of Fgf-signaling demonstrated that this pathway regulates cell proliferation across all three limb axes, in contrast to anurans and amniotes where Fgf-signaling regulates cell survival and proximodistal patterning.https://elifesciences.org/articles/48507limb developmentSonic hedgehogfibroblast growth factorsalamandermorphogenesis
spellingShingle Sruthi Purushothaman
Ahmed Elewa
Ashley W Seifert
Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development
eLife
limb development
Sonic hedgehog
fibroblast growth factor
salamander
morphogenesis
title Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development
title_full Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development
title_fullStr Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development
title_full_unstemmed Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development
title_short Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development
title_sort fgf signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development
topic limb development
Sonic hedgehog
fibroblast growth factor
salamander
morphogenesis
url https://elifesciences.org/articles/48507
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AT ahmedelewa fgfsignalingiscompartmentalizedwithinthemesenchymeandcontrolsproliferationduringsalamanderlimbdevelopment
AT ashleywseifert fgfsignalingiscompartmentalizedwithinthemesenchymeandcontrolsproliferationduringsalamanderlimbdevelopment