Cell cycle controls and the role of nerves and the regenerate epithelium in urodele forelimb regeneration: possible modifications of basic concepts

Data from pulse and continuous labeling with [3H]thymidine and from studies with monoclonal antibody WE3 have led to the modification of existing models and established concepts pertinent to understanding limb regeneration. Not all cells of the adult newt blastema are randomly distributed and actively progressing through the cell cycle. Instead, many cells are in a position that we have designated transient quiescence (TQ) and are not actively cycling. We postulate that cells regularly leave the TQ population and enter the actively cycling population and vice versa. The size of the TQ population may be at least partly determined by the quantity of limb innervation. Larval Ambystoma may have only a small or nonexisting TQ, thus accounting for their rapid rate of regeneration. Examination of reactivity of monoclonal antibody WE3 suggests that the early wound epithelium, which is derived from skin epidermis, is later replaced by cells from skin glands concomitant with blastema formation. WE3 provides a useful tool to further investigate the regenerate epithelium.

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Regeneration and pattern formation in planarians. II. and role of cell movements in blastema formation

Development ◽

10.1242/dev.107.1.69 ◽

1989 ◽

Vol 107 (1) ◽

pp. 69-76 ◽

Cited By ~ 1

Author(s):

E. Salo ◽

J. Baguna

Keyword(s):

Pattern Formation ◽

Cell Movement ◽

Formation Mechanisms ◽

Blastema Formation ◽

Chromosomal Markers ◽

Undifferentiated Cells ◽

Local Cell ◽

Number Of Cells ◽

Wound Epithelium

In planarians, blastema cells do not divide, and growth blastema is thought to result from the steady wound epithelium, of undifferentiated cells produced in the stump. However, whether these cells come only sources or whether cells placed far from the wound can participate, after long-range migrations, in the still uncertain. To study this problem, we have parameters of the process of regeneration: cell growth; number of cells produced by mitosis in the wound (postblastema); and rates of movement undifferentiated cells using grafting procedures with chromosomal markers. The results show that: (1) cells area spread (move) at higher rates than cells placed (90–140_mday-1 versus 40–50_mday-1); (2) cells than 500_m from the wound boundary are hardly 5-day-old blastemata; and (3) the number of cells within a 200–300_m postblastema area around the wound explain, provided their rates of movement are taken increasing number of blastema cells. From this, it is blastema cells in planarians originate from local mitotic activity jointly with local cell movement postblastema area around the wound match the blastema cells during regeneration. The implications for blastema growth and pattern formation mechanisms

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Inhibition of BMP and FGF signaling prior to wound epithelium formation leads to an aberrant regenerative response in teleost fish Poecilia latipinna

10.1101/2021.01.27.428424 ◽

2021 ◽

Author(s):

Isha Ranadive ◽

Sonam Patel ◽

Siddharth Pai ◽

Kashmira Khaire ◽

Suresh Balakrishnan

Keyword(s):

Cell Death ◽

Teleost Fish ◽

The Other ◽

Fgf Signaling ◽

Caudal Fin ◽

Fin Regeneration ◽

Blastema Formation ◽

Messenger Molecules ◽

Wound Epithelium

The BMP and FGF pathways play a pivotal role in the successful regeneration of caudal fin of teleost fish. Individual inhibition of these pathways led to impaired caudal fin regeneration until the pharmacologic inhibitor of FGF (SU5402) and BMP (LDN193189) were metabolized off. Therefore, in the current study both these pathways were inhibited collectively wherein inhibition of BMP and FGF during the wound epithelium formation led to stalling of the process by bringing down the established levels of shh and runx2. In members of the treatment group, it was observed that, each blastema grows crouched rather than linear and the regrown lepidotrichia therefore remain tilted down. Amongst the other irregularities observed, the transition from epithelial to mesenchymal cells was found hindered due to down-regulation of snail and twist, brought about by BMP and FGF inhibition. Compromised expression of Snail and twist deranged the normal levels of cadherins causing disruption in the transition of cells. Lastly, blocking BMP and FGF delayed blastema formation and proliferation due to diminished levels of fgf2, fgf8, fgf10 and bmp6, while casp3 and casp9 levels remained heightened causing accelerated cell death. This study not only highlights the axial role of BMP and FGF pathways in regeneration but also accentuates the collaboration amongst the two. This ingenious coordination of signalling further reinforces the involvement of relaying messenger molecules between these crucial pathways.

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Limb Regeneration in Amphibians: Immunological Considerations

The Scientific World JOURNAL ◽

10.1100/tsw.2006.323 ◽

2006 ◽

Vol 6 ◽

pp. 1-11 ◽

Cited By ~ 40

Author(s):

Anthony L. Mescher ◽

Anton W. Neff

Keyword(s):

Limb Regeneration ◽

Regenerative Capacity ◽

Anuran Amphibians ◽

Regenerative Growth ◽

Key Aspects ◽

Regeneration Blastema ◽

Wound Epithelium

We review key aspects of what is known about limb regeneration in urodele and anuran amphibians, with a focus on the early events of the process that lead to formation of the regeneration blastema. This includes the role of the nerves and wound epithelium, but also covers the inflammatory effects of the amputation trauma and their importance for regenerative growth. We propose that immunotolerance is important for limb regeneration and changes in its regulation may underlie the loss of regenerative capacity during anuran metamorphosis.

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Role of pRB dephosphorylation in cell cycle regulation

Frontiers in Bioscience ◽

10.2741/a501 ◽

2000 ◽

Vol 5 (3) ◽

pp. d121-137 ◽

Cited By ~ 4

Author(s):

John W Ludlow

Keyword(s):

Cell Cycle ◽

Cell Cycle Regulation ◽

Cycle Regulation

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Biological Role of CDK 11 and 12 in Cell Cycle and its Function in Tumorigenesis

Pakistan Journal of Medicine and Dentistry ◽

10.36283/pjmd9-3/020 ◽

2020 ◽

Author(s):

Shamim Mushtaq

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Web Of Science ◽

The Body ◽

Main Role ◽

Hallmarks Of Cancer ◽

Cyclin Dependent Kinases ◽

Tumor Studies ◽

Cycle Regulation

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.

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PTTG has a Dual Role of Promotion-Inhibition in the Development of Pituitary Adenomas

Protein and Peptide Letters ◽

10.2174/0929866526666190722145449 ◽

2019 ◽

Vol 26 (11) ◽

pp. 800-818

Author(s):

Zujian Xiong ◽

Xuejun Li ◽

Qi Yang

Keyword(s):

Cell Cycle ◽

Pituitary Adenoma ◽

Pituitary Adenomas ◽

Cell Cycle Progression ◽

Key Factors ◽

Cycle Progression ◽

Sister Chromatids ◽

Regulation Of Cell Cycle ◽

Late Stages

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

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