Evidence map›Paper›PMID 19948009›Full record

ArticleBMC biology2009

Proteomic analysis of blastema formation in regenerating axolotl limbs.

Nandini Rao, Deepali Jhamb, Derek J Milner, Bingbing Li, Fengyu Song, Mu Wang, S Randal Voss, Mathew Palakal, Michael W King, Behnaz Saranjami and 3 more

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 145 citations in OpenAlex.

  1. bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. The endocannabinoid system regulates both ependymoglial and neuronal cell responses to a tail amputation in the axolotl.Developmental dynamics : an official publication of the American Association of Anatomists · 2026
    Article
  4. Extracellular matrix remodeling supportsbioRxiv : the preprint server for biology · 2025
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. The salamander blastema within the broader context of metazoan regeneration.Frontiers in cell and developmental biology · 2023
    Review
  17. Local problems need global solutions: The metabolic needs of regenerating organisms.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2022
    Review
  18. Evi5 is required forFrontiers in cell and developmental biology · 2022
    Article
  19. Review
  20. Review

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Nandini RaoDepartment of Biology and Center for Regenerative Biology and Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA. narao@iupui.edu
Deepali Jhamb
Derek J Milner
Bingbing Li
Fengyu Song
Mu Wang
S Randal Voss
Mathew Palakal
Michael W King
Behnaz Saranjami
Holly L D Nye
Jo Ann Cameron
David L Stocum
Indiana University – Purdue University Indianapolis · USUniversity of Illinois Urbana-Champaign · USUniversity of Indianapolis · USUniversity of Kentucky · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFollowing amputation, urodele salamander limbs reprogram somatic cells to form a blastema that self-organizes into the missing limb parts to restore the structure and function of the limb. To help understand the molecular basis of blastema formation, we used quantitative label-free liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)-based methods to analyze changes in the proteome that occurred 1, 4 and 7 days post amputation (dpa) through the mid-tibia/fibula of axolotl hind limbs.

resultsWe identified 309 unique proteins with significant fold change relative to controls (0 dpa), representing 10 biological process categories: (1) signaling, (2) Ca2+ binding and translocation, (3) transcription, (4) translation, (5) cytoskeleton, (6) extracellular matrix (ECM), (7) metabolism, (8) cell protection, (9) degradation, and (10) cell cycle. In all, 43 proteins exhibited exceptionally high fold changes. Of these, the ecotropic viral integrative factor 5 (EVI5), a cell cycle-related oncoprotein that prevents cells from entering the mitotic phase of the cell cycle prematurely, was of special interest because its fold change was exceptionally high throughout blastema formation.

conclusionOur data were consistent with previous studies indicating the importance of inositol triphosphate and Ca2+ signaling in initiating the ECM and cytoskeletal remodeling characteristic of histolysis and cell dedifferentiation. In addition, the data suggested that blastema formation requires several mechanisms to avoid apoptosis, including reduced metabolism, differential regulation of proapoptotic and antiapoptotic proteins, and initiation of an unfolded protein response (UPR). Since there is virtually no mitosis during blastema formation, we propose that high levels of EVI5 function to arrest dedifferentiated cells somewhere in the G1/S/G2 phases of the cell cycle until they have accumulated under the wound epidermis and enter mitosis in response to neural and epidermal factors. Our findings indicate the general value of quantitative proteomic analysis in understanding the regeneration of complex structures.

Indexed as

ProteomicsAmbystomaAmputation, SurgicalAnimalsCalcium SignalingChromatography, High Pressure LiquidExtracellular MatrixExtremitiesInositol 1,4,5-TrisphosphatePeptide MappingRegenerationTandem Mass SpectrometryWound HealingInositol 1,4,5-Trisphosphate

Identifiers

PMID19948009
PMCPMC2794268
OpenAlexW2143924854

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.