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Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb

BACKGROUND: The bat has strikingly divergent forelimbs (long digits supporting wing membranes) and hindlimbs (short, typically free digits) due to the distinct requirements of both aerial and terrestrial locomotion. During embryonic development, the morphology of the bat forelimb deviates dramatical...

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Autores principales: Mason, Mandy K, Hockman, Dorit, Curry, Lyle, Cunningham, Thomas J, Duester, Gregg, Logan, Malcolm, Jacobs, David S, Illing, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389300/
https://www.ncbi.nlm.nih.gov/pubmed/25861444
http://dx.doi.org/10.1186/s13227-015-0001-y
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author Mason, Mandy K
Hockman, Dorit
Curry, Lyle
Cunningham, Thomas J
Duester, Gregg
Logan, Malcolm
Jacobs, David S
Illing, Nicola
author_facet Mason, Mandy K
Hockman, Dorit
Curry, Lyle
Cunningham, Thomas J
Duester, Gregg
Logan, Malcolm
Jacobs, David S
Illing, Nicola
author_sort Mason, Mandy K
collection PubMed
description BACKGROUND: The bat has strikingly divergent forelimbs (long digits supporting wing membranes) and hindlimbs (short, typically free digits) due to the distinct requirements of both aerial and terrestrial locomotion. During embryonic development, the morphology of the bat forelimb deviates dramatically from the mouse and chick, offering an alternative paradigm for identifying genes that play an important role in limb patterning. RESULTS: Using transcriptome analysis of developing Natal long-fingered bat (Miniopterus natalensis) fore- and hindlimbs, we demonstrate that the transcription factor Meis2 has a significantly higher expression in bat forelimb autopods compared to hindlimbs. Validation by reverse transcriptase and quantitative polymerase chain reaction (RT-qPCR) and whole mount in situ hybridisation shows that Meis2, conventionally known as a marker of the early proximal limb bud, is upregulated in the bat forelimb autopod from CS16. Meis2 expression is localised to the expanding interdigital webbing and the membranes linking the wing to the hindlimb and tail. In mice, Meis2 is also expressed in the interdigital region prior to tissue regression. This interdigital Meis2 expression is not activated by retinoic acid (RA) signalling as it is present in the retained interdigital tissue of Rdh10(trex/trex) mice, which lack RA. Additionally, genes encoding RA-synthesising enzymes, Rdh10 and Aldh1a2, and the RA nuclear receptor Rarβ are robustly expressed in bat fore- and hindlimb interdigital tissues indicating that the mechanism that retains interdigital tissue in bats also occurs independently of RA signalling. CONCLUSIONS: Mammalian interdigital Meis2 expression, and upregulation in the interdigital webbing of bat wings, suggests an important role for Meis2 in autopod development. Interdigital Meis2 expression is RA-independent, and retention of interdigital webbing in bat wings is not due to the suppression of RA-induced cell death. Rather, RA signalling may play a role in the thinning (rather than complete loss) of the interdigital tissue in the bat forelimb, while Meis2 may interact with other factors during both bat and mouse autopod development to maintain a pool of interdigital cells that contribute to digit patterning and growth. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13227-015-0001-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-43893002015-04-09 Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb Mason, Mandy K Hockman, Dorit Curry, Lyle Cunningham, Thomas J Duester, Gregg Logan, Malcolm Jacobs, David S Illing, Nicola EvoDevo Research BACKGROUND: The bat has strikingly divergent forelimbs (long digits supporting wing membranes) and hindlimbs (short, typically free digits) due to the distinct requirements of both aerial and terrestrial locomotion. During embryonic development, the morphology of the bat forelimb deviates dramatically from the mouse and chick, offering an alternative paradigm for identifying genes that play an important role in limb patterning. RESULTS: Using transcriptome analysis of developing Natal long-fingered bat (Miniopterus natalensis) fore- and hindlimbs, we demonstrate that the transcription factor Meis2 has a significantly higher expression in bat forelimb autopods compared to hindlimbs. Validation by reverse transcriptase and quantitative polymerase chain reaction (RT-qPCR) and whole mount in situ hybridisation shows that Meis2, conventionally known as a marker of the early proximal limb bud, is upregulated in the bat forelimb autopod from CS16. Meis2 expression is localised to the expanding interdigital webbing and the membranes linking the wing to the hindlimb and tail. In mice, Meis2 is also expressed in the interdigital region prior to tissue regression. This interdigital Meis2 expression is not activated by retinoic acid (RA) signalling as it is present in the retained interdigital tissue of Rdh10(trex/trex) mice, which lack RA. Additionally, genes encoding RA-synthesising enzymes, Rdh10 and Aldh1a2, and the RA nuclear receptor Rarβ are robustly expressed in bat fore- and hindlimb interdigital tissues indicating that the mechanism that retains interdigital tissue in bats also occurs independently of RA signalling. CONCLUSIONS: Mammalian interdigital Meis2 expression, and upregulation in the interdigital webbing of bat wings, suggests an important role for Meis2 in autopod development. Interdigital Meis2 expression is RA-independent, and retention of interdigital webbing in bat wings is not due to the suppression of RA-induced cell death. Rather, RA signalling may play a role in the thinning (rather than complete loss) of the interdigital tissue in the bat forelimb, while Meis2 may interact with other factors during both bat and mouse autopod development to maintain a pool of interdigital cells that contribute to digit patterning and growth. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13227-015-0001-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-14 /pmc/articles/PMC4389300/ /pubmed/25861444 http://dx.doi.org/10.1186/s13227-015-0001-y Text en © Mason et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Mason, Mandy K
Hockman, Dorit
Curry, Lyle
Cunningham, Thomas J
Duester, Gregg
Logan, Malcolm
Jacobs, David S
Illing, Nicola
Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb
title Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb
title_full Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb
title_fullStr Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb
title_full_unstemmed Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb
title_short Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb
title_sort retinoic acid-independent expression of meis2 during autopod patterning in the developing bat and mouse limb
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389300/
https://www.ncbi.nlm.nih.gov/pubmed/25861444
http://dx.doi.org/10.1186/s13227-015-0001-y
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