Transcriptional factor Pitx2: Localization during triton retina regeneration

Markitantova

2016

Biomedicines

Many regeneration processes in animals are based on the phenomenon of cell reprogramming followed by proliferation and differentiation in a different specialization direction. An insight into what makes natural (in vivo) cell reprogramming possible can help to solve a number of biomedical problems. In particular, the first problem is to reveal the intrinsic properties of the cells that are necessary and sufficient for reprogramming; the second, to evaluate these properties and, on this basis, to reveal potential endogenous sources for cell substitution in damaged tissues; and the third, to use the acquired data for developing approaches to in vitro cell reprogramming in order to obtain a cell reserve for damaged tissue repair. Normal cells of the retinal pigment epithelium (RPE) in newts (Urodela) can change their specialization and transform into retinal neurons and ganglion cells (i.e., actualize their retinogenic potential). Therefore, they can serve as a model that provides the possibility to identify factors of the initial competence of vertebrate cells for reprogramming in vivo. This review deals mainly with the endogenous properties of native newt RPE cells themselves and, to a lesser extent, with exogenous mechanisms regulating the process of reprogramming, which are actively discussed.

Section: Regeneration Of Neural Retina (Nr) From Retinal Pigmentedmentioning

confidence: 99%

Section: Transcription Factors and Signal Molecules Characteristicmentioning

confidence: 99%

Cellular and Molecular Preconditions for Retinal Pigment Epithelium (RPE) Natural Reprogramming during Retinal Regeneration in Urodela

Markitantova

2016

Biomedicines

“…We have detected the expression of the Pax6 gene, along with other TFs and signaling molecules, in the retina as links in the regulatory network of the “eye field” during retinal development [ 55 ]. These factors were also identified during retinal regeneration from RPE [ 52 , 71 , 72 , 73 ]. The co-expression of key molecules of the melanogenic (Otx2) and pro-neural (Pax6, Pitx1(2)) differentiations, as well as signaling regulators (Fgf2 и FgfR2), indicates the probability of “combined” expression of the marker molecules of specific RPE differentiation and the factors regulating the early eye development [ 54 , 55 , 73 ].…”

Section: Specifics Of Eye and Brain Tissues And Their Regenerationmentioning

confidence: 99%

Study of Natural Longlife Juvenility and Tissue Regeneration in Caudate Amphibians and Potential Application of Resulting Data in Biomedicine

2021

JDB

The review considers the molecular, cellular, organismal, and ontogenetic properties of Urodela that exhibit the highest regenerative abilities among tetrapods. The genome specifics and the expression of genes associated with cell plasticity are analyzed. The simplification of tissue structure is shown using the examples of the sensory retina and brain in mature Urodela. Cells of these and some other tissues are ready to initiate proliferation and manifest the plasticity of their phenotype as well as the correct integration into the pre-existing or de novo forming tissue structure. Without excluding other factors that determine regeneration, the pedomorphosis and juvenile properties, identified on different levels of Urodele amphibians, are assumed to be the main explanation for their high regenerative abilities. These properties, being fundamental for tissue regeneration, have been lost by amniotes. Experiments aimed at mammalian cell rejuvenation currently use various approaches. They include, in particular, methods that use secretomes from regenerating tissues of caudate amphibians and fish for inducing regenerative responses of cells. Such an approach, along with those developed on the basis of knowledge about the molecular and genetic nature and age dependence of regeneration, may become one more step in the development of regenerative medicine

“…A study of gene expression in CMZ cells in caudate amphibians, e.g., the newt Pleurodeles waltl , demonstrated the progenitor status of cells in this zone that are involved, along with RPE (see below), in retinal regeneration. The expression of TFs belonging to the EFTF group (Pax6, Otx2, and Six3, as well as c-myc, Prox1, and Pitx2) was also detected [ 51 , 52 , 53 ]. When we saturated adult newt CMZ cells with BrdU, a proliferation marker, this showed that 15–20% of CMZ cells were in the phase of DNA synthesis within a month after the artificial retinal detachment [ 54 ].…”

Section: Eye Ciliary Zonementioning

confidence: 99%

“…The main events on the pathway of this transformation are as follows: the exit of cells from the RPE layer, their proliferation with the loss of the initial phenotypic features, the formation of a population of cells with neuroblast features, and then their differentiation with the recovery to a fully functioning retina ( Figure 6 and Figure 7 ). All these stages are described from the aspect of cell biology and variations in the expression of genes of newt eye RPE cells [ 51 , 52 , 53 , 119 , 120 , 121 , 122 , 123 ].…”

Section: Retinal Pigment Epitheliummentioning

confidence: 99%

Potential Endogenous Cell Sources for Retinal Regeneration in Vertebrates and Humans: Progenitor Traits and Specialization

2020

Biomedicines

Retinal diseases often cause the loss of photoreceptor cells and, consequently, impairment of vision. To date, several cell populations are known as potential endogenous retinal regeneration cell sources (RRCSs): the eye ciliary zone, the retinal pigment epithelium, the iris, and Müller glia. Factors that can activate the regenerative responses of RRCSs are currently under investigation. The present review considers accumulated data on the relationship between the progenitor properties of RRCSs and the features determining their differentiation. Specialized RRCSs (all except the ciliary zone in low vertebrates), despite their differences, appear to be partially “prepared” to exhibit their plasticity and be reprogrammed into retinal neurons due to the specific gene expression and epigenetic landscape. The “developmental” characteristics of RRCS gene expression are predefined by the pathway by which these cell populations form during eye morphogenesis; the epigenetic features responsible for chromatin organization in RRCSs are under intracellular regulation. Such genetic and epigenetic readiness is manifested in vivo in lower vertebrates and in vitro in higher ones under conditions permissive for cell phenotype transformation. Current studies on gene expression in RRCSs and changes in their epigenetic landscape help find experimental approaches to replacing dead cells through recruiting cells from endogenous resources in vertebrates and humans.