Nail-associated mesenchymal cells contribute to and are essential for dorsal digit tip regeneration

Mahmud, Neemat; Eisner, Christine; Purushothaman, Sruthi; Storer, Mekayla; Kaplan, David R.; Miller, Freda D.

doi:10.1016/j.celrep.2022.111853

Cited by 8 publications

(2 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies in non-mammalian epimorphic limb regeneration models, such as the axolotl, demonstrate that limb connective tissue is the main contributor of both cells and patterning information to the blastema ( Stocum, 1982 ; Muneoka et al, 1986a ; Muneoka et al, 1986b ; Lin et al, 2021 ). In the context of the mouse digit tip, the term “connective tissue” broadly encompasses heterogeneous fibroblasts [including mesenchymal progenitors, reticular fibroblasts, nail bed mesenchyme, and nerve-associated mesenchyme ( Wu et al, 2013 ; Marrero et al, 2017 ; Carr et al, 2019 ; Johnson et al, 2020 ; Mahmud et al, 2022 )], and skeletal cells [including tendon-associated cells, periosteal cells, and bone-associated cells ( Lee et al, 2013 ; Dawson et al, 2016 ; Johnson et al, 2020 )]. Failure of digit tip regeneration following genetic deletion of Msx1 or conditional ablation of Pdgfrα-expressing cells supports the importance of connective tissue for this process ( Han et al, 2003 ; Storer et al, 2020 ).…”

Section: Connective Tissue and Extracellular Matrix During Regenerationmentioning

confidence: 99%

“…Fibroblasts make up the majority of cells in the digit tip blastema ( Johnson et al, 2020 ). Both immunohistochemistry and single cell RNA sequencing-based analyses demonstrate extensive heterogeneity among this population, suggestive of diversity in function during regeneration ( Marrero et al, 2017 ; Carr et al, 2019 ; Johnson et al, 2020 ; Storer et al, 2020 ; Mahmud et al, 2022 ). One of these functions is to serve as a cellular source, i.e., progenitor cells, for regenerating connective tissues.…”

Section: Connective Tissue and Extracellular Matrix During Regenerationmentioning

confidence: 99%

See 1 more Smart Citation

Toeing the line between regeneration and fibrosis

Jou

Lehoczky

2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Understanding the remarkable capacity of vertebrates to naturally regenerate injured body parts has great importance for potential translation into human therapeutic applications. As compared to other vertebrates, mammals have low regenerative capacity for composite tissues like the limb. However, some primates and rodents can regenerate the distal tips of their digits following amputation, indicating that at least very distal mammalian limb tissues are competent for innate regeneration. It follows that successful digit tip regenerative outcome is highly dependent on the location of the amputation; those proximal to the position of the nail organ do not regenerate and result in fibrosis. This distal regeneration versus proximal fibrosis duality of the mouse digit tip serves as a powerful model to investigate the driving factors in determining each process. In this review, we present the current understanding of distal digit tip regeneration in the context of cellular heterogeneity and the potential for different cell types to function as progenitor cells, in pro-regenerative signaling, or in moderating fibrosis. We then go on to discuss these themes in the context of what is known about proximal digit fibrosis, towards generating hypotheses for these distinct healing processes in the distal and proximal mouse digit.

show abstract

Section: Connective Tissue and Extracellular Matrix During Regenerationmentioning

confidence: 99%

Section: Connective Tissue and Extracellular Matrix During Regenerationmentioning

confidence: 99%

Toeing the line between regeneration and fibrosis

Jou

Lehoczky

2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

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

Castilla‐Ibeas,

Zdral,

Oberg

et al. 2024

Developmental Dynamics

View full text Add to dashboard Cite

The limb anatomy displays well‐defined dorsal and ventral compartments, housing extensor, and flexor muscles, which play a crucial role in facilitating limb locomotion and manipulation. Despite its importance, the study of limb dorsoventral patterning has been relatively neglected compared to the other two axes leaving many crucial questions about the genes and developmental processes implicated unanswered. This review offers a thorough overview of the current understanding of limb dorsoventral patterning, synthesizing classical literature with recent research. It covers the specification of dorsal fate in the limb mesoderm and its subsequent translation into dorsal morphologies—a process directed by the transcription factor Lmx1b. We also discuss the potential role of dorsoventral patterning in the evolution of paired appendages and delve into the involvement of LMX1B in Nail‐Patella syndrome, discussing the molecular and genetic aspects underlying this condition. Finally, the potential role of dorsoventral polarity in digit tip regeneration, a prominent instance of multi‐tissue regeneration in mammals is also considered. We anticipate that this review will renew interest in a process that is critical to limb function and evolutionary adaptations but has nonetheless been overlooked.

Nail-associated mesenchymal cells contribute to and are essential for dorsal digit tip regeneration

Cited by 8 publications

References 52 publications

Toeing the line between regeneration and fibrosis

Toeing the line between regeneration and fibrosis

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

Nail mesenchyme: Tipping the hand on regeneration

Contact Info

Product

Resources

About