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Experience-Dependent Transfer of Otx2 Homeoprotein into the Visual Cortex Activates Postnatal Plasticity
Open accessAbstract
Neural circuits are shaped by experience in early postnatal life. Distinct GABAergic connections within visual cortex determine the timing of the critical period for rewiring ocular dominance to establish visual acuity. We find that maturation of the parvalbumin (PV)-cell network that controls plasticity onset is regulated by a selective re-expression of the embryonic Otx2 homeoprotein. Visual experience promoted the accumulation of non-cell-autonomous Otx2 in PV-cells, and cortical infusion of exogenous Otx2 accelerated both PV-cell development and critical period timing. Conversely, conditional removal of Otx2 from non-PV cells or from the visual pathway abolished plasticity. Thus, the experience-dependent transfer of a homeoprotein may establish the physiological milieu for postnatal plasticity of a neural circuit.
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In the citing paper
“On the other hand, an experience-dependent accumulation of exogenous OTX2, a homeoprotein commonly bound to PNNs and PV1 cells in the mPFC (Lee et al., 2017), is necessary for the formation of PNNs and critical period closure in the visual cortex (Sugiyama et al., 2008).”
From Perineuronal Nets Regulate the Inhibitory Perisomatic Input onto Parvalbumin Interneurons and γ Activity in the Prefrontal Cortex (2020) · cites this paper as Sugiyama et al., 2008
In the citing paper
“For example, reductions of inhibitory neural activity in adulthood have increased visual plasticity in rodents (He et al., 2007, Sugiyama et al., 2008, Harauzov et al., 2010) and even restored visual function in amblyopic adult rats (Vetencourt et al., 2008).”
From The impact of developmental timing for stress and recovery (2015) · cites this paper as Sugiyama et al., 2008
In the citing paper
“Accordingly, disruption of E-I balance powerfully shifts the timing and quality of critical period development, as seen in the primary visual cortex (V1) (27–29).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [27]
In the citing paper
“Second, PNN disruption prevents the persistent uptake of Otx2 homeoprotein into the enwrapped PV-cells required for their maintenance (27, 40, 41) (Fig. S3).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [27]
In the citing paper
“Compromised PNNs prevent the persistent uptake of Otx2 homeoprotein into the enwrapped PV-cells needed for their maturation (including PNN maintenance itself) (27, 40, 41).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [27]
In the citing paper
“Blocking Otx2 transport in the retina (between bipolar cells and retinal ganglion cells) or in the cortex (by directly infusing anti-Otx2 antibodies) retards the activity-dependent opening of CP in the visual cortex (Sugiyama et al., 2008).”
From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Sugiyama et al., 2008
In the citing paper
“In support of the hypothesis is that direct infusion of Otx2 before CP opening opens CP ahead of time and also closes it ahead of time (Sugiyama et al., 2008).”
From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Sugiyama et al., 2008
In the citing paper
“Moreover, the opening of plasticity (first threshold) does not take place in dark-reared animals, where the Otx2 and PV levels remain low in PV-cells.”
From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Sugiyama et al., 2008
In the citing paper
“Accordingly, we showed that Otx2 injected in the eye can travel along this pathway and terminates in PV-cells (Sugiyama et al., 2008; Sugiyama et al., 2009).”
From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Sugiyama et al., 2008
In the citing paper
“Subsequent Otx2 internalization increases intracellular Otx2 and PV-cell maturation reflected by further PV expression and PNN assembly (Sugiyama et al., 2008) until a second threshold is reached that closes plasticity.”
From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Sugiyama et al., 2008
In the citing paper
“Instead, PV-cell maturation in dark-reared animals is rescued by direct Otx2 infusion leading to its specific accumulation in PV-cells and CP opening (Sugiyama et al., 2008).”
From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Sugiyama et al., 2008
In the citing paper
“Otx2 expression coincides with both PV and PNN expression in the cortex during critical period plasticity (Sugiyama et al., 2008).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Sugiyama et al., 2008
In the citing paper
“PNNs also regulate PV cell maturation via internalization of homeoprotein Otx2, which is needed for transcription, normal PV development and critical period plasticity in developing visual cortex (Sugiyama et al. 2008).”
From Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice (2018) · cites this paper as Sugiyama et al. 2008
In the citing paper
“this homeoprotein signals the maturation of the parvalbumin-containing GABAergic interneurons, which contributes to the opening and possibly also the closure of the critical period”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Sugiyama et al., 2008
In the citing paper
“PNNs also facilitate the capture and uptake of the transcription factor Otx2, which in turn promotes PVBC maturation as well as further PNN development (100, 173, 912, 1063).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1063]
In the citing paper
“PNNs also facilitate the capture and uptake of the transcription factor Otx2, which in turn promotes PVBC maturation as well as further PNN development (100, 173, 912, 1063).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1063]
In the citing paper
“The maturation of cortical inhibitory networks in the postnatal brain is important for initiating this critical period (Fagiolini and Hensch, 2000; Sugiyama et al., 2008).”
From Clock Genes Control Cortical Critical Period Timing (2015) · cites this paper as Sugiyama et al., 2008
In the citing paper
“Acceleration of PV-cell maturation by over-expressing non-cell-autonomous factors, such as brain-derived neurotrophic factor (BDNF) or orthodenticle homeobox 2 (Otx2), induces precocious plasticity (Huang et al., 1999; Sugiyama et al., 2008).”
From Clock Genes Control Cortical Critical Period Timing (2015) · cites this paper as Sugiyama et al., 2008
In the citing paper
“PNNs have been linked to the transcription factor orthodenticle homeobox protein 2 (OTX2) (35)”
From Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity (2019) · cites this paper as [35]
In the citing paper
“Additionally, OTX2 has been shown to specifically accumulate in PV+ cells through exogenous transfer from the choroid plexus, the region where it is produced (35; 46).”
From Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity (2019) · cites this paper as [35]
In the citing paper
“Orthodenticle homeobox protein 2 (OTX2) is a transcription factor known to be important in the regulation of the critical period of plasticity in the visual cortex of developing mice (46) and its expression coincides with the maturation of PV+ cells and the closure of the critical period (35).”
From Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity (2019) · cites this paper as [35]
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“From our data, the cortical appearance of non-cell autonomous Otx2 requires visual input; however, retinal Otx2 synthesis does not (Sugiyama et al. 2008).”
BackgroundInfluentialSelf-citationDiverse functions of perineuronal nets
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“PNN regression and reinstates juvenile plasticity (Sugiyama et al., 2008; Beurdeley et al., 2012).”
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“The classical delay of OD plasticity by CDR can be prevented by directly enhancing inhibition in the dark: by infusion of benzodiazepines (Iwai et al., 2003), Otx2 homeoprotein (Sugiyama et al., 2008), or genetic overexpression of BDNF (Gianfranceschi et al., 2003).”
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“The non-cell-autonomous hypothesis has been verified in vivo for the homeoproteins Pax6, Otx2 and Engrailed (Layalle et al., 2011; Lesaffre et al., 2007; Sugiyama et al., 2008).”
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“Digestion of CSPGs in visual cortex removes molecular inhibitors of anatomical plasticity (Pizzorusso et al., 2002, 2006; Orlando et al., 2012), and these molecules are also required for PV interneurons to capture the transcription factor Otx2 (Sugiyama et al., 2008).”
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“Intracortical infusion of Otx2 accelerates PV-cell development and the timing of the critical period, whereas deletion of Otx2 prevents the onset of the critical period (67).”
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“…analyzed the density of PV+ INs in a pre-CP stage (postnatal day P18), at the transition toward the opening of the CP (postnatal day P21), and at the end of the CP (postnatal day P35) (Fagiolini et al., 2004; Hooks and Chen, 2007; Sugiyama et al., 2008; Levelt and Hübener, 2012; Sun et al., 2016).”
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“As this increase does not take place in the dark, it must also be activity dependent (Sugiyama et al., 2008).”
InfluentialSelf-citationIGF-1 Restores Visual Cortex Plasticity in Adult Life by Reducing Local GABA Levels
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“One prominent example is a non-cell autonomous role of the Otx2 homeoprotein in experience-dependent plasticity (Sugiyama et al., 2008).”
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Self-citationEngrailed homeoprotein acts as a signaling molecule in the developing fly
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“Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity.”
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“Sugiyama et al. (2008) showed that TCAs from the dLG nucleus play a key role in mediating experience-dependent maturation of inhibitory circuits in V1 during the critical period of ocular dominance plasticity (Sugiyama et al., 2008).”
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“Visual experience signals the time-course of the CP by promoting the transfer of the protein Otx2 from the retina to the VC, where Otx2 promotes the maturation of parvalbumin-positive GABAergic interneurons (Sugiyama et al. 2008).”
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“critical period depends on the accumulation of OTX2 in parvalbumin-containing interneurons (109).”
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“This hypothesis was confirmed by the fact that Otx2 directly infused into the cortex accumulates preferentially into PV-cells, not only in the course of postnatal plasticity, but also in the adult (Sugiyama et al., 2008).”
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“Accordingly, the impairment of plasticity in Otx2-knockout animals is rescued by enhancing GABA-A receptor currents by benzodiazepine treatments [22].”
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“…the fascinating finding that the transcription factor OTX2 which is transcribed and translated in the retina is transported transsynaptically to V1 where it is taken up predominantly by PV basket cells and a small percentage of other interneuron subtypes where it stimulates their development [32].”
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“In the cortex, OTX2 is specifically internalized by parvalbumin interneurons, which have a unique and stable ECM called perineuronal nets (PNNs) that often stain for the lectin Wisteria floribunda agglutinin (WFA; Sugiyama et al., 2008).”
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“…of critical periods, the increased formation of PNNs is thought to regulate the fast-spiking activity of PV neurons and lead to their maturation and decreased plasticity by controlling the extracellular concentrations of ions and other regulatory molecules (Hensch, 2005; Sugiyama et al., 2008).”
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“In addition to Brn3a, -synuclein has been used to identify RGCs (Soto et al., 2008; Surgucheva et al., 2008).”
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“Similar effects of dark rearing have been described for ocular dominance plasticity (Cynader and Mitchell, 1980; Mower et al., 1981; Morales et al., 2002; Pizzorusso et al., 2002; Maffei, 2008; Sugiyama et al., 2008).”
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“The experience-dependent maturation of PV circuits opens the CP in V1 (Sugiyama et al., 2008) and plays a similar role in other brain areas (Spatazza et al., 2013).”
BackgroundSelf-citationPerineuronal Nets: Subtle Structures with Large Implications
Carceller, H., Gramuntell, Y., Klimczak, P., & Nácher, J. (2022) · The Neuroscientist · doi:10.1177/10738584221106346 · Cited by 54
Effects of Digesting Chondroitin Sulfate Proteoglycans on Plasticity in Cat Primary Visual Cortex
Vorobyov, V., Kwok, J. C. F., Fawcett, J. W., & Sengpiel, F. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2283-12.2013 · Cited by 51
“…acid decarboxylase (Harauzov et al., 2010), re-expression of the embryonic Otx2 homeoprotein in parvalbumin-positive cells in adult visual cortex (Sugiyama et al., 2008), treatment with the serotonin reuptake inhibitor fluoxetine (Maya Vetencourt et al., 2008), and enhancement of nicotinic…”
BackgroundCadet, J. L., Jayanthi, S., McCoy, M. T., Ladenheim, B., Saint-Preux, F., Lehrmann, E., De, S., Becker, K. G., & Brannock, C. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-545 · Cited by 50
“Our observations are also consistent with the idea that drug addiction is dependent on altered synaptic plasticity [93-96] that are regulated, in part, by developmental factors in adult animals [91,97].”
BackgroundRibic, A., Crair, M. C., & Biederer, T. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.069 · Cited by 51
“Otx2, a PNN-dependent transcription factor that directs the maturation of PV + interneurons (Sugiyama et al., 2008), was un-altered in SynCAM 1-KO PV + interneurons (Figure S3).”
BackgroundTegla, M. G. G., Buenaventura, D. F., Kim, D. Y., Thakurdin, C., Gonzalez, K. C., & Emerson, M. M. (2020) · eLife · doi:10.7554/elife.54279 · Cited by 50
“Thus, there could be OTX2-positive cells outside of the OTX2ECR2 population that are affected by the gene editing plasmid, and therefore a formal possibility that these mutated cells have a cell non-autonomous effect on the OTX2ECR2 population, either through changes in secreted factors, or through OTX2 itself, which…”
BackgroundBrief dark exposure restored ocular dominance plasticity in aging mice and after a cortical stroke
Stodieck, S. K., Greifzu, F., Goetze, B., Schmidt, K.-F., & Löwel, S. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.09.007 · Cited by 43
Deletion of Otx2 in GnRH Neurons Results in a Mouse Model of Hypogonadotropic Hypogonadism
Diaczok, D., DiVall, S. A., Matsuo, I., Wondisford, F. E., Wolfe, A., & Radovick, S. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0271 · Cited by 53
Self-citationSimonetti, T., Lee, H., Bourke, M. J., Leamey, C. A., & Sawatari, A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006780 · Cited by 50
Graded Otx2 activities demonstrate dose-sensitive eye and retina phenotypes
Bernard, C., Kim, H.-T., Torero Ibad, R., Lee, E. J., Simonutti, M., Picaud, S., Acampora, D., Simeone, A., Di Nardo, A. A., Prochiantz, A., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt562 · Cited by 39
“However, in this context, it is important to note that Otx2 is captured by RGCs where the Otx2 locus is silent and that blocking Otx2 transfer, probably from bipolar cells, retards the opening of the critical period for binocular vision (11).”
Self-citationPathological plasticity in fragile X syndrome.
Martin, B. S., & Huntsman, M. M. (2012) · Neural Plasticity · doi:10.1155/2012/275630 · Cited by 57
Epigenetic regulation of brain development, plasticity, and response to early-life stress
Peña, C. J. (2025) · Neuropsychopharmacology · doi:10.1038/s41386-025-02179-z · Cited by 56
“However, DNA methylation at other plasticity-related genes was found to be altered by child abuse and mediate depression, including at the NMDA receptor gene GRIN1 [128], and at OTX2 [129], a transcription factor involved in neural development and critical period plasticity [130].”
Large-Scale Axonal Reorganization of Inhibitory Neurons following Retinal Lesions
Marik, S. A., Yamahachi, H., Borgloh, S. M. Z. A., & Gilbert, C. D. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4345-13.2014 · Cited by 46
The Physiology of Homeoprotein Transduction
Nardo, A. A. D., Fuchs, J., Joshi, R. L., Moya, K. L., & Prochiantz, A. (2018) · Physiological Reviews · doi:10.1152/physrev.00018.2017 · Cited by 52
Self-citationAccelerated Hyper-Maturation of Parvalbumin Circuits in the Absence of MeCP2
Patrizi, A., Awad, P. N., Chattopadhyaya, B., Li, C., Di Cristo, G., & Fagiolini, M. (2020) · Cerebral Cortex · doi:10.1093/cercor/bhz085 · Cited by 46
“For example, brain-derived neurotrophic factor (BDNF) and homeoprotein Otx2 (orthodenticle homeobox 2) contribute to the structural and functional maturation of PV cells (Huang et al. 1999; Sugiyama et al. 2008; Riffault et al. 2014).”
BackgroundNon-cell Autonomous OTX2 Homeoprotein Regulates Visual Cortex Plasticity Through Gadd45b/g
Apulei, J., Kim, N., Testa, D., Ribot, J., Morizet, D., Bernard, C., Jourdren, L., Blugeon, C., Nardo, A. A. D., & Prochiantz, A. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy108 · Cited by 51
Self-citationContinued growth and circuit building in the anamniote visual system
Cerveny, K. L., Varga, M., & Wilson, S. W. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20917 · Cited by 45
“Recent studies in mice have illustrated that trans-synaptic transfer of the homeodomain protein, Otx2, is required throughout the visual system during the mammalian critical period, stimulating visual circuit formation and remodeling in the visual cortex (Sugiyama et al., 2008).”
BackgroundMaturation of "Neocortex Isole" In Vivo in Mice
Zhou, L., Gall, D., Qu, Y., Prigogine, C., Cheron, G. A., Tissir, F., Schiffmann, S. N., & Goffinet, A. M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.6005-09.2010 · Cited by 46
“…mutants survive up to days 20 – 21, when cortical laminar and areal development is basically complete, but before the onset of the critical period (Sugiyama et al., 2008), allowing for the first time the investigation of cortical maturation in the absence of extracortical connections, a…”
BackgroundMethodCallosal contribution to ocular dominance in rat primary visual cortex
Cerri, C., Restani, L., & Caleo, M. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07363.x · Cited by 46
“Indeed, it is well known that thalamic afferents directly contact and activate GABAergic interneurons in primary sensory cortex (Erisir & Dreusicke, 2005; Cruikshank et al., 2007; Sugiyama et al., 2008).”
BackgroundTranscriptional regulation of tangential neuronal migration in the developing forebrain
Chédotal, A., & Rijli, F. M. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.04.005 · Cited by 45
The Determination of Rod and Cone Photoreceptor Fate
Cepko, C. L. (2015) · Annual Review of Vision Science · doi:10.1146/annurev-vision-090814-121657 · Cited by 48
“Because Otx2 is expressed in multiple retinal cell types and in the retinal pigment epithelium (RPE), and because the Otx2 protein can be taken up by cells that do not express it (Sugiyama et al. 2008), it is currently unclear whether such effects resulted fromdevelopmental or later effects andwhether these effects we…”
BackgroundYoshioka, N., Miyata, S., Tamada, A., Watanabe, Y., Kawasaki, A., Kitagawa, H., Takao, K., Miyakawa, T., Takeuchi, K., & Igarashi, M. (2017) · Molecular Brain · doi:10.1186/s13041-017-0328-5 · Cited by 45
“PNNs modulate synaptic functions, particularly GABAergic inhibitory input via parvalbumin (PV) (+) neuronal cells [1].”
Baho, E., Chattopadhyaya, B., Lavertu-Jolin, M., Mazziotti, R. M., Awad, P. N., Chehrazi, P., Groleau, M., Jahannault-Talignani, C., Sanon, N. T., Vaucher, E., et al. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.2881-18.2019 · Cited by 44
“…may directly affect the stability of PV cell axonal branches and synapses by affecting local cytoskeletal dynamics (Deinhardt et al., 2011; Sun et al., 2012) or/and affect the synthesis of specific proteins, including those required for PNN condensation around PV-positive cells (Carulli…”
BackgroundLullo, E. D., Haton, C., Poupon, C. L., Volovitch, M., Joliot, A., Thomas, J., & Prochiantz, A. (2011) · Development · doi:10.1242/dev.066282 · Cited by 45
“In the visual cortex, the HP Otx2 is specifically internalized by a particular subset of interneurons containing the Ca2+-binding protein parvalbumin (Sugiyama et al., 2008).”
BackgroundSelf-citationSárvári, M., Kalló, I., Hrabovszky, E., Solymosi, N., Rodolosse, A., & Liposits, Z. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00149 · Cited by 48
Chondroitin sulfate proteoglycans in neural development and plasticity
Maeda, N. (2010) · Frontiers in Bioscience · doi:10.2741/3637 · Cited by 44
Rath, M. F., Bailey, M. J., Kim, J., Coon, S. L., Klein, D. C., & Møller, M. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05765.x · Cited by 43
Impaired Processing in the Primary Auditory Cortex of an Animal Model of Autism
Anomal, R. F., de Villers‐Sidani, E., Brandão, J. A., Diniz, R. M. B., Costa, M. R., & Romcy-Pereira, R. N. (2015) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00158 · Cited by 46
“Interestingly, these animals also display, altered GABAergic signaling associated to an acoustic hypersensitivity Frontiers in Systems Neuroscience | www.frontiersin.org 8 November 2015 | Volume 9 | Article 158 and propensity for audiogenic seizures (D’Hulst et al., 2006; Rotschafer and Razak, 2013).”
BackgroundInfluentialMechanisms of Plasticity in the Developing and Adult Visual Cortex
Sur, M., Nagakura, I., Chen, N., & 杉原, 弘. (2013) · Progress in brain research · doi:10.1016/b978-0-444-63327-9.00002-3 · Cited by 44
Morishita, H., Kundakovic, M., Bicks, L., Mitchell, A., & Akbarian, S. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2015.03.005 · Cited by 42
Mapping the mosaic sequence of primate visual cortical development
Mundiñano, I.-C., Kwan, W. C., & Bourne, J. A. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00132 · Cited by 41
“…neuronal proliferation (Fernando et al., 2011), migration (López-Bendito et al., 2003; Manent et al., 2005), synaptic wiring (Di Cristo et al., 2004; Wu et al., 2012), cortical synchrony (Sohal et al., 2009), and plasticity (Huang et al., 1999; Fagiolini and Hensch, 2000; Sugiyama et al., 2008).”
BackgroundTreatment of amblyopia in the adult: insights from a new rodent model of visual perceptual learning
Bonaccorsi, J., Berardi, N., & Sale, A. (2014) · Frontiers in Neural Circuits · doi:10.3389/fncir.2014.00082 · Cited by 42
“That is, in addition to the occurrence of a CP for the establishment of amblyopia, there is also a sensitive period for a successful treatment of this pathology (see Lewis and Maurer, 2009).”
BackgroundInfluentialNoncanonical intracrine action
Ré, R. N., & Cook, J. L. (2011) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2011.07.001 · Cited by 41
Bernard, C., Vincent, C., Testa, D., Bertini, E., Ribot, J., Nardo, A. A. D., Volovitch, M., & Prochiantz, A. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006035 · Cited by 55
Self-citationThe endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7
Trofimenko, E., Homma, Y., Fukuda, M., & Widmann, C. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109945 · Cited by 44
“Additionally, HPs, such as Engrailed 2 and OTX2, exhibit therapeutic properties (Alvarez-Fischer et al., 2011; Blaudin de Thé et al., 2018; Rekaik et al., 2015a; Rekaik et al., 2015b; Sugiyama et al., 2008; Torero Ibad et al., 2011).”
BackgroundMizumoto, S., & Yamada, S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.764781 · Cited by 43
“Furthermore, Otx2, which is a homeoprotein and regulates ocular dominance plasticity via its effects on maturation of parvalbumin-expressing interneurons (Sugiyama et al., 2008), diffused and reduced at the surrounding parvalbumin-expressing interneurons in Chst3-transgenic mice (Miyata et al.”
BackgroundExpression of the homeobox genes PAX6, OTX2, and OTX1 in the early human fetal retina
Larsen, K. B., Lutterodt, M. C., Rath, M. F., & Møller, M. (2009) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2009.04.004 · Cited by 43
“Thus Sugiyama et al. (2008) have recently demonstrated that the Otx2 protein in the mouse is transported trans-synaptically in the optic system from the retina to the visual cortex, where the protein can modify postnatal plasticity.”
Meng, J., Ma, X., Tao, H., Jin, X. M., Witvliet, D. K., Mitchell, J. K., Zhu, M., Dong, M., Zhen, M., Jin, Y., et al. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.03.022 · Cited by 39
“Overexpressing orthodenticle homeobox 2 (Otx2) in parvalbumin (PV)-expressing cells induces precocious visual plasticity, while reducing Otx2 uptake in PV cells reopens plasticity in adulthood (Sugiyama et al., 2008).”
BackgroundBenchmarking brain organoid recapitulation of fetal corticogenesis
Cheroni, C., Trattaro, S., Caporale, N., Tobon, A., Tenderini, E., Sebastiani, S., Troglio, F., Gabriele, M., Bressan, R. B., Pollard, S. M., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02279-0 · Cited by 43
Critical aspects of neurodevelopment
Chakraborty, R., Kumar, M., & Clement, J. P. (2021) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2021.107415 · Cited by 41
The mechanisms of perineuronal net abnormalities in contributing aging and neurological diseases
Dong, Y., Zhao, K., Qin, X., Du, G., & Gao, L. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102092 · Cited by 39
Sydnor, V. J., Bagautdinova, J., Larsen, B., Arcaro, M. J., Barch, D. M., Bassett, D. S., Alexander‐Bloch, A. F., Cook, P. A., Covitz, S. C., Franco, A. R., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01991-6 · Cited by 57
“During early post-natal development, experience-dependent transfer of homeoproteins from the thalamus to cortical PV interneurons impacts the timing of sensory cortex critical periods 50 .”
Bitanihirwe, B. K. Y., Mauney, S. A., & Woo, T.-U. W. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.03.1047 · Cited by 40
Neural ECM in regeneration and rehabilitation
Yang, S., Kwok, J. C. F., & Fawcett, J. W. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63486-3.00008-6 · Cited by 37
Cortical GABAergic Interneurons in Cross-Modal Plasticity following Early Blindness
Desgent, S., & Ptito, M. (2012) · Neural Plasticity · doi:10.1155/2012/590725 · Cited by 41
“PV neurons) and modulate critical period plasticity [22, 151, 185, 192, 193].”
BackgroundSantos‐Silva, T., Colodete, D. A. E., Lisboa, J. R., Freitas, I. D. S., Lopes, C. F. B., Hadera, V., Lima, T. S. A., Souza, A. J., & Gomes, F. V. (2024) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13994 · Cited by 39
“18 Various peptides and CSPG mimetics can block the transfer of Otx2 into the PV interneuron nucleus, modulating gene expression implicated in PV interneuron maturation and PNNs formation.”
BackgroundWhite, S. A. (2009) · Brain and Language · doi:10.1016/j.bandl.2009.10.002 · Cited by 37
Mainardi, M., Landi, S., Berardi, N., Maffei, L., & Pizzorusso, T. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004342 · Cited by 36
Durieux, L. J. A., Gilissen, S. R. J., & Arckens, L. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15110 · Cited by 40
Mueller-Buehl, C., Reinhard, J., Roll, L., Bader, V., Winklhofer, K. F., & Faissner, A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.886527 · Cited by 37
Amblyopia: Background to the special issue on stroke recovery
Maurer, D. M., & Hensch, T. K. (2012) · Developmental Psychobiology · doi:10.1002/dev.21022 · Cited by 40
“, 2004), by prematurely boosting brain-derived neurotropic factor (BDNF) levels (Hanover, Huang, Tonegawa, & Stryker, 1999), or by particular homeoprotein transcription factors (Otx2), all of which accelerate the maturation of specific GABA circuits, the perisomatic, large basket cell (Sugiyama et al., 2008).”
BackgroundSelf-citationA postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons
Moissidis, M., Abbasova, L., Selten, M. M., Alis, R., Bernard, C., Domínguez-Canterla, Y., Oozeer, F., Qin, S., Kelly, A., Mòdol, L., et al. (2025) · Cell · doi:10.1016/j.cell.2025.06.029 · Cited by 38
Metadata
- Authors
- Sugiyama, S., Di Nardo, A. A., Aizawa, S., Matsuo, I., Volovitch, M., Prochiantz, A., & Hensch, T. K.
- Affiliations
- Boston Children's Hospital (US)
- RIKEN (JP)
- Osaka Women's and Children's Hospital (JP)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Prochiantz, Alain
- Hensch, Takao K.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 134
- Issue
- 3
- Pages
- 508-520
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2150947848
- Cited by
- 491
- References
- 76
- Citations by year
- 2026: 11 · 2025: 23 · 2024: 22 · 2023: 23 · 2022: 16 · 2021: 32 · 2020: 33 · 2019: 25 · 2018: 26 · 2017: 31 · 2016: 20 · 2015: 38 · 2014: 42 · 2013: 41 · 2012: 28
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1847 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Otx2, homeoproteins, parvalbumin interneurons, visual cortex, critical period, ocular dominance, visual experience, GABAergic circuits, neural circuit development
- MeSH terms
- Animals, Humans, Interneurons, Neuronal Plasticity, Parvalbumins, Recombinant Proteins, Sensory Deprivation, Visual Cortex, Visual Pathways, Mice, Otx Transcription Factors
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