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En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration

The mouse digit tip regenerates following amputation. How the regenerate is patterned is unknown, but a long-standing hypothesis proposes developmental patterning mechanisms are re-used during regeneration. The digit tip bone exhibits dorsal-ventral (DV) polarity, so we focus on En1 and Lmx1b, two f...

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Autores principales: Johnson, Gemma L., Glasser, Morgan B., Charles, Julia F., Duryea, Jeffrey, Lehoczky, Jessica A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727699/
https://www.ncbi.nlm.nih.gov/pubmed/36417876
http://dx.doi.org/10.1016/j.celrep.2022.111701
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author Johnson, Gemma L.
Glasser, Morgan B.
Charles, Julia F.
Duryea, Jeffrey
Lehoczky, Jessica A.
author_facet Johnson, Gemma L.
Glasser, Morgan B.
Charles, Julia F.
Duryea, Jeffrey
Lehoczky, Jessica A.
author_sort Johnson, Gemma L.
collection PubMed
description The mouse digit tip regenerates following amputation. How the regenerate is patterned is unknown, but a long-standing hypothesis proposes developmental patterning mechanisms are re-used during regeneration. The digit tip bone exhibits dorsal-ventral (DV) polarity, so we focus on En1 and Lmx1b, two factors necessary for DV patterning during limb development. We investigate whether they are re-expressed during regeneration in a developmental-like pattern and whether they direct DV morphology of the regenerate. We find that both En1 and Lmx1b are expressed in the regenerating digit tip epithelium and mesenchyme, respectively, but without DV polarity. Conditional genetics and quantitative analysis of digit tip bone morphology determine that genetic deletion of En1 or Lmx1b in adult digit tip regeneration modestly reduces bone regeneration but does not affect DV patterning. Collectively, our data suggest that, while En1 and Lmx1b are re-expressed during mouse digit tip regeneration, they do not define the DV axis during regeneration.
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spelling pubmed-97276992022-12-07 En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration Johnson, Gemma L. Glasser, Morgan B. Charles, Julia F. Duryea, Jeffrey Lehoczky, Jessica A. Cell Rep Article The mouse digit tip regenerates following amputation. How the regenerate is patterned is unknown, but a long-standing hypothesis proposes developmental patterning mechanisms are re-used during regeneration. The digit tip bone exhibits dorsal-ventral (DV) polarity, so we focus on En1 and Lmx1b, two factors necessary for DV patterning during limb development. We investigate whether they are re-expressed during regeneration in a developmental-like pattern and whether they direct DV morphology of the regenerate. We find that both En1 and Lmx1b are expressed in the regenerating digit tip epithelium and mesenchyme, respectively, but without DV polarity. Conditional genetics and quantitative analysis of digit tip bone morphology determine that genetic deletion of En1 or Lmx1b in adult digit tip regeneration modestly reduces bone regeneration but does not affect DV patterning. Collectively, our data suggest that, while En1 and Lmx1b are re-expressed during mouse digit tip regeneration, they do not define the DV axis during regeneration. 2022-11-22 /pmc/articles/PMC9727699/ /pubmed/36417876 http://dx.doi.org/10.1016/j.celrep.2022.111701 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-Nd license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Johnson, Gemma L.
Glasser, Morgan B.
Charles, Julia F.
Duryea, Jeffrey
Lehoczky, Jessica A.
En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration
title En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration
title_full En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration
title_fullStr En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration
title_full_unstemmed En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration
title_short En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration
title_sort en1 and lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727699/
https://www.ncbi.nlm.nih.gov/pubmed/36417876
http://dx.doi.org/10.1016/j.celrep.2022.111701
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