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En1 和 Lmx1b 在小鼠趾尖再生过程中不能再现胚胎背腹肢模式形成的功能。

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

机构信息

Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.

出版信息

Cell Rep. 2022 Nov 22;41(8):111701. doi: 10.1016/j.celrep.2022.111701.


DOI:10.1016/j.celrep.2022.111701
PMID:36417876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9727699/
Abstract

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.

摘要

鼠标指尖在截肢后会再生。目前尚不清楚再生是如何形成模式的,但一个长期存在的假设提出,在再生过程中会重新利用发育模式形成机制。指尖骨表现出背腹(DV)极性,因此我们专注于 En1 和 Lmx1b,这两个因子在肢体发育过程中对于 DV 模式形成是必需的。我们研究它们是否在再生过程中以类似发育的模式重新表达,以及它们是否指导再生的 DV 形态。我们发现,En1 和 Lmx1b 分别在再生的指尖上皮和间充质中表达,但没有 DV 极性。对指尖骨形态的条件遗传学和定量分析确定,成年指尖再生中 En1 或 Lmx1b 的基因缺失适度减少了骨再生,但不影响 DV 模式形成。总的来说,我们的数据表明,尽管 En1 和 Lmx1b 在小鼠指尖再生过程中重新表达,但它们在再生过程中并不确定 DV 轴。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/b5e0937a153b/nihms-1852533-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/9d151b6a97df/nihms-1852533-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/1c89af5dd708/nihms-1852533-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/c49e770f041d/nihms-1852533-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/de095d4c4993/nihms-1852533-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/4b4be842150c/nihms-1852533-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/b5e0937a153b/nihms-1852533-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/9d151b6a97df/nihms-1852533-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/1c89af5dd708/nihms-1852533-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/c49e770f041d/nihms-1852533-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/de095d4c4993/nihms-1852533-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/4b4be842150c/nihms-1852533-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3112/9727699/b5e0937a153b/nihms-1852533-f0007.jpg

相似文献

[1]
En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration.

Cell Rep. 2022-11-22

[2]
Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity.

Cell Rep. 2023-1-31

[3]
Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs.

Development. 1998-3

[4]
The limb dorsoventral axis: Lmx1b's role in development, pathology, evolution, and regeneration.

Dev Dyn. 2024-9

[5]
Nail-associated mesenchymal cells contribute to and are essential for dorsal digit tip regeneration.

Cell Rep. 2022-12-20

[6]
Lmx1b activation in axolotl limb regeneration.

Dev Dyn. 2022-9

[7]
Uncoupling skeletal and connective tissue patterning: conditional deletion in cartilage progenitors reveals cell-autonomous requirements for Lmx1b in dorsal-ventral limb patterning.

Development. 2010-4

[8]
BMP controls proximodistal outgrowth, via induction of the apical ectodermal ridge, and dorsoventral patterning in the vertebrate limb.

Development. 2001-11

[9]
Lmx1b-expressing cells in the mouse limb bud define a dorsal mesenchymal lineage compartment.

Genesis. 2009-4

[10]
Bone growth as the main determinant of mouse digit tip regeneration after amputation.

Sci Rep. 2019-7-4

引用本文的文献

[1]
How axolotl cells 'remember' development to rebuild a lost limb.

Nature. 2025-5-21

[2]
Versican controlled by Lmx1b regulates hyaluronate density and hydration for semicircular canal morphogenesis.

Development. 2025-1-1

[3]
Regeneration-specific promoter switching facilitates Mest expression in the mouse digit tip to modulate neutrophil response.

NPJ Regen Med. 2024-10-28

[4]
Regeneration-specific promoter switching facilitates Mest expression in the mouse digit tip to modulate neutrophil response.

bioRxiv. 2024-6-15

[5]
Versican controlled by Lmx1b regulates hyaluronate density and hydration for semicircular canal morphogenesis.

bioRxiv. 2024-5-8

[6]
The development of hair follicles and nail.

Dev Biol. 2024-9

[7]
Lgr6-expressing functional nail stem-like cells differentiated from human-induced pluripotent stem cells.

PLoS One. 2024

[8]
A screen for regeneration-associated silencer regulatory elements in zebrafish.

Dev Cell. 2024-3-11

[9]
The limb dorsoventral axis: Lmx1b's role in development, pathology, evolution, and regeneration.

Dev Dyn. 2024-9

[10]
In conversation with Freda Miller.

Nat Neurosci. 2023-10

本文引用的文献

[1]
Single-cell resolution of MET- and EMT-like programs in osteoblasts during zebrafish fin regeneration.

iScience. 2022-1-19

[2]
Mammalian Digit Tip Regeneration: Moving from Phenomenon to Molecular Mechanism.

Cold Spring Harb Perspect Biol. 2022-1-4

[3]
Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs.

Development. 2021-6-1

[4]
Transcriptomic analysis of bone and fibrous tissue morphogenesis during digit tip regeneration in the adult mouse.

FASEB J. 2020-7

[5]
Remembering where we are: Positional information in salamander limb regeneration.

Dev Dyn. 2020-4

[6]
Cellular Heterogeneity and Lineage Restriction during Mouse Digit Tip Regeneration at Single-Cell Resolution.

Dev Cell. 2020-2-24

[7]
Acquisition of a Unique Mesenchymal Precursor-like Blastema State Underlies Successful Adult Mammalian Digit Tip Regeneration.

Dev Cell. 2020-1-2

[8]
Hierarchical pattern formation during amphibian limb regeneration.

Biosystems. 2019-9

[9]
Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration.

Science. 2018-9-27

[10]
Blastema formation and periosteal ossification in the regenerating adult mouse digit.

Wound Repair Regen. 2018-5

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