Postnatal signalling with homeoprotein transcription factors

Prochiantz, Alain; Fuchs, Julia; Nardo, Ariel A. Di

doi:10.1098/rstb.2013.0518

Cited by 13 publications

(7 citation statements)

References 33 publications

(66 reference statements)

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“…Thus, the stabilization of PNNs in learning centers may underlie the shift from malleable to resilient memory storage in these brains structures. Maintaining this stabilized state, in turn, appears to require continuous, brain-wide access to non-cell-autonomous Otx2 protein (Spatazza et al 2013;Prochiantz et al 2014).…”

Section: Otx2mentioning

confidence: 99%

Developmental pathway genes and neural plasticity underlying emotional learning and stress-related disorders

Maheu

Ressler

2017

Learn. Mem.

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The manipulation of neural plasticity as a means of intervening in the onset and progression of stress-related disorders retains its appeal for many researchers, despite our limited success in translating such interventions from the laboratory to the clinic. Given the challenges of identifying individual genetic variants that confer increased risk for illnesses like depression and post-traumatic stress disorder, some have turned their attention instead to focusing on so-called "master regulators" of plasticity that may provide a means of controlling these potentially impaired processes in psychiatric illnesses. The mammalian homolog of (TLX), Wnt, and the homeoprotein Otx2 have all been proposed to constitute master regulators of different forms of plasticity which have, in turn, each been implicated in learning and stress-related disorders. In the present review, we provide an overview of the changing distribution of these genes and their roles both during development and in the adult brain. We further discuss how their distinct expression profiles provide clues as to their function, and may inform their suitability as candidate drug targets in the treatment of psychiatric disorders.

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Section: Otx2mentioning

confidence: 99%

Developmental pathway genes and neural plasticity underlying emotional learning and stress-related disorders

Maheu

Ressler

2017

Learn. Mem.

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“…Given the reported negative effect of CNTF on electrical response in the mouse retina, the effect observed by grafting cells overexpressing OTX2 might be unrelated to the upregulation of CNTF 51 . Alternatively, we could not rule out that the effect on cones is mediated by OTX2, because it has been shown to mediate paracrine effects in the retina 52 …”

Section: Discussionmentioning

confidence: 98%

Otx2-Genetically Modified Retinal Pigment Epithelial Cells Rescue Photoreceptors after Transplantation

et al. 2018

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Inherited retinal degenerations are blinding diseases characterized by the loss of photoreceptors. Their extreme genetic heterogeneity complicates treatment by gene therapy. This has motivated broader strategies for transplantation of healthy retinal pigmented epithelium to protect photoreceptors independently of the gene causing the disease. The limited clinical benefit for visual function reported up to now is mainly due to dedifferentiation of the transplanted cells that undergo an epithelial-mesenchymal transition. We have studied this mechanism in vitro and revealed the role of the homeogene OTX2 in preventing dedifferentiation through the regulation of target genes. We have overexpressed OTX2 in retinal pigmented epithelial cells before their transplantation in the eye of a model of retinitis pigmentosa carrying a mutation in Mertk, a gene specifically expressed by retinal pigmented epithelial cells. OTX2 increases significantly the protection of photoreceptors as seen by histological and functional analyses. We observed that the beneficial effect of OTX2 is non-cell autonomous, and it is at least partly mediated by unidentified trophic factors. Transplantation of OTX2-genetically modified cells may be medically effective for other retinal diseases involving the retinal pigmented epithelium as age-related macular degeneration.

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“…Thus, to optimize the rehabilitative processes discussed here, it would seem pertinent to, when possible, take advantage of the optimal plasticity that exists during each critical period, for each visual attribute. Unfortunately, this is presently difficult given the time course of the critical period is known for only two visual attributes ( binocular vision and acuity ); (e) rodent models have allowed identifying neuro-chemical changes that control the onset of the critical period for binocular vision, as well as molecular and structural brakes that lead to the diminution of the plasticity thereafter (e.g., Hensch, 2005 ; Sugiyama et al, 2008 , 2009 ; Hensch and Bilimoria, 2012 ; Prochiantz et al, 2014 ; Prochiantz and Di Nardo, 2015 ; Bernard and Prochiantz, 2016 for reviews). However, no application of these findings has been developed for humans yet, as far as we are aware.…”

Section: Discussionmentioning

confidence: 99%

Beyond Rehabilitation of Acuity, Ocular Alignment, and Binocularity in Infantile Strabismus

Milleret

Quoc

2018

Front. Syst. Neurosci.

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Infantile strabismus impairs the perception of all attributes of the visual scene. High spatial frequency components are no longer visible, leading to amblyopia. Binocularity is altered, leading to the loss of stereopsis. Spatial perception is impaired as well as detection of vertical orientation, the fastest movements, directions of movement, the highest contrasts and colors. Infantile strabismus also affects other vision-dependent processes such as control of postural stability. But presently, rehabilitative therapies for infantile strabismus by ophthalmologists, orthoptists and optometrists are restricted to preventing or curing amblyopia of the deviated eye, aligning the eyes and, whenever possible, preserving or restoring binocular vision during the critical period of development, i.e., before ~10 years of age. All the other impairments are thus ignored; whether they may recover after strabismus treatment even remains unknown. We argue here that medical and paramedical professionals may extend their present treatments of the perceptual losses associated with infantile strabismus. This hypothesis is based on findings from fundamental research on visual system organization of higher mammals in particular at the cortical level. In strabismic subjects (as in normal-seeing ones), information about all of the visual attributes converge, interact and are thus inter-dependent at multiple levels of encoding ranging from the single neuron to neuronal assemblies in visual cortex. Thus if the perception of one attribute is restored this may help to rehabilitate the perception of other attributes. Concomitantly, vision-dependent processes may also improve. This could occur spontaneously, but still should be assessed and validated. If not, medical and paramedical staff, in collaboration with neuroscientists, will have to break new ground in the field of therapies to help reorganize brain circuitry and promote more comprehensive functional recovery. Findings from fundamental research studies in both young and adult patients already support our hypothesis and are reviewed here. For example, presenting different contrasts to each eye of a strabismic patient during training sessions facilitates recovery of acuity in the amblyopic eye as well as of 3D perception. Recent data also demonstrate that visual recoveries in strabismic subjects improve postural stability. These findings form the basis for a roadmap for future research and clinical development to extend presently applied rehabilitative therapies for infantile strabismus.

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Postnatal signalling with homeoprotein transcription factors

Cited by 13 publications

References 33 publications

Developmental pathway genes and neural plasticity underlying emotional learning and stress-related disorders

Developmental pathway genes and neural plasticity underlying emotional learning and stress-related disorders

Otx2-Genetically Modified Retinal Pigment Epithelial Cells Rescue Photoreceptors after Transplantation

Beyond Rehabilitation of Acuity, Ocular Alignment, and Binocularity in Infantile Strabismus

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