In vitro effects of insulin on macromolecular events in newt limb regeneration blastemata

Vethamany‐Globus, Swani; Globus, Morton; Darch, A.; Milton, G.; Tomlinson, Bruce L.

doi:10.1002/jez.1402310109

Cited by 13 publications

(4 citation statements)

References 37 publications

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“…During this transition phase, positional identity is regained and signaling to activate progenitor cells that are required to initiate growth occurs. Insulin growth factor (IGF) signaling was first implicated in limb regeneration in newts over three decades ago (Vethamany-Globus, 1987;Vethamany-Globus et al, 1984). More recently, it was Cohort names correspond to conditions illustrated in Fig.…”

Section: Discussion Molecular Signatures Indicate Conserved Features mentioning

confidence: 99%

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

et al. 2017

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Here we present a parallel study of mRNA and microRNA expression during oral siphon (OS) regeneration in Ciona robusta, and the derived network of their interactions. In the process of identifying 248 mRNAs and 15 microRNAs as differentially expressed, we also identified 57 novel microRNAs, several of which are among the most highly differentially expressed. Analysis of functional categories identified enriched transcripts related to stress responses and apoptosis at the wound healing stage, signaling pathways including Wnt and TGFβ during early regrowth, and negative regulation of extracellular proteases in late stage regeneration. Consistent with the expression results, we found that inhibition of TGFβ signaling blocked OS regeneration. A correlation network was subsequently inferred for all predicted microRNA-mRNA target pairs expressed during regeneration. Network-based clustering associated transcripts into 22 non-overlapping groups, the functional analysis of which showed enrichment of stress response, signaling pathway and extracellular protease categories that could be related to specific microRNAs. Predicted targets of the miR-9 cluster suggest a role in regulating differentiation and the proliferative state of neural progenitors through regulation of the cytoskeleton and cell cycle.

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Section: Discussion Molecular Signatures Indicate Conserved Features mentioning

confidence: 99%

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

et al. 2017

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“…In addition to a lack of evidence for the existence of "an integral entity" of a "hormonal background" specific to regeneration, this model simply fails to deal with the available data on specific actions of hormones such as INS in regenerating blastema (17,18). The HM model implies passive hormone participation as en masse and collectively treats the mere existence of a pool of hormones in the milieu as a single activating unit.…”

Section: "Hormonal Milieu" Modelmentioning

confidence: 90%

“…Based solely on our in vivo and in vitro findings that INS is an essential hormone in newt limb regeneration and that a combination of INS, GH, hydrocortisone, and THY maximizes cell proliferation and growth or innervated blastemal cultures (17,18,(24)(25)(26), it has now become customary to include INS alone or a combination of the above-mentioned hormones in cultures of blastemal tissues to promote cell proliferation and growth (27). Unfortunately, in interpreting the results from these experiments, there is a tendency to consider INS and other hormones as passive ingredients and to ignore the active, synergistic role(s) that these hormones might play, along with nerves in the parameter being measured.…”

Section: Addition Of Hormones To Blastema Culturesmentioning

confidence: 99%

Hormone action in newt limb regeneration: insulin and endorphins

Vethamany‐Globus

1987

Biochem. Cell Biol.

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Although several hormones have been linked to newt limb regeneration, a cohesive hypothesis as to how these hormones control the process is yet to emerge. A critical review of the traditional approaches and a reevaluation of currently operative assumptions and interpretations of results precede the data on insulin and beta-endorphin. Results from in vivo and in vitro experiments on insulin are summarized, showing that insulin not only promotes various cellular events but also is essential for the expression of the mitogenic effect of nerves on cultured newt limb blastemata. Furthermore, the strong likelihood that insulin may be the common link in promoting limb regeneration in hypophysectomized newts that received pituitary hormone replacement therapy or a nutritional supplement is discussed. The status of beta-endorphin in regeneration is also explored. Data are presented to show that vertebrates with regenerating capacity (newts, tadpoles) have higher levels of plasma beta-endorphin than that found in species where the capacity to regenerate is either restricted (frogs) or totally lost (mammals). beta-Endorphin-like immunoreactivity has been localized in the epidermis of a regenerating newt blastema, as well as in the intermediate lobe of the pituitary gland of axolotl, newt, and Xenopus. A possible opiate connection in vertebrate limb regeneration, in particular, wound healing, is discussed.

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“…However, systemic or long-range factors have also been implicated in appendage regeneration beyond the local structures of wound epidermis, nerves, and blastema cells, though decidedly less mechanistic information exists on systemic factors. For example, the thyroid gland, the pituitary gland, and the pancreas have all separately been demonstrated to be required for salamander limb regeneration [106–112]. Transcriptomic evidence suggests involvement of thyroid hormone signaling in lizard tail regeneration as well [113].…”

Section: Systemic Inputs In Appendage Regenerationmentioning

confidence: 99%

Common themes in tetrapod appendage regeneration: a cellular perspective

Miller

Johnson²,

Whited³

2019

EvoDevo

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Complete and perfect regeneration of appendages is a process that has fascinated and perplexed biologists for centuries. Some tetrapods possess amazing regenerative abilities, but the regenerative abilities of others are exceedingly limited. The reasons underlying these differences have largely remained mysterious. A great deal has been learned about the morphological events that accompany successful appendage regeneration, and a handful of experimental manipulations can be reliably applied to block the process. However, only in the last decade has the goal of attaining a thorough molecular and cellular biological understanding of appendage regeneration in tetrapods become within reach. Advances in molecular and genetic tools for interrogating these remarkable events are now allowing for unprecedented access to the fundamental biology at work in appendage regeneration in a variety of species. This information will be critical for integrating the large body of detailed observations from previous centuries with a modern understanding of how cells sense and respond to severe injury and loss of body parts. Understanding commonalities between regenerative modes across diverse species is likely to illuminate the most important aspects of complex tissue regeneration.

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In vitro effects of insulin on macromolecular events in newt limb regeneration blastemata

Cited by 13 publications

References 37 publications

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

Hormone action in newt limb regeneration: insulin and endorphins

Common themes in tetrapod appendage regeneration: a cellular perspective

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