Extracellular Pax6 Regulates Tangential Cajal–Retzius Cell Migration in the Developing Mouse Neocortex

Kaddour, Hadhemi; Coppola, Eva; Nardo, Ariel A. Di; Poupon, Chantal Le; Mailly, Phillipe; Wizenmann, Andrea; Volovitch, Michel; Prochiantz, Alain; Pierani, Alessandra

doi:10.1093/cercor/bhz098

Cited by 15 publications

(15 citation statements)

References 31 publications

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“…The capacity of a large number of homeoproteins to transfer is less of an open question despite the initial focus on only few homeoproteins. Non-cell-autonomous in vivo activity has been reported for EN1/2, PAX6, OTX2, KN1, several HOXs, and VAX1 (10,27,34,35,45,(65)(66)(67)(68)(69)(70), while all in vitro studies addressing the cellular mechanisms of transfer were done mainly with EN2. The hypothesis that most homeoproteins transfer in vivo is now supported by systematic assays involving 160 diverse homeoproteins in which intracellular transfer was confirmed for more than 150 homeoproteins both in HeLa cells and in mouse embryonic brain (13).…”

Section: Generalization Of Homeoprotein Intercellular Transfermentioning

confidence: 99%

Homeoprotein transduction in neurodevelopment and physiopathology

2020

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Homeoproteins were originally identified for embryonic cell–autonomous transcription activity, but they also have non–cell-autonomous activity owing to transfer between cells. This Review discusses transfer mechanisms and focuses on some established functions, such as neurodevelopmental regulation of axon guidance, and postnatal critical periods of brain plasticity that affect sensory processing and cognition. Homeoproteins are present across all eukaryotes, and intercellular transfer occurs in plants and animals. Proposed functions have evolutionary relevance, such as morphogenetic activity and sexual exchange during the mating of unicellular eukaryotes, while others have physiopathological relevance, such as regulation of mood and cognition by influencing brain compartmentalization, connectivity, and plasticity. There are more than 250 known homeoproteins with conserved transfer domains, suggesting that this is a common mode of signal transduction but with many undiscovered functions.

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Section: Generalization Of Homeoprotein Intercellular Transfermentioning

confidence: 99%

Homeoprotein transduction in neurodevelopment and physiopathology

2020

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“…As an additional control, we also evaluated PV Cre ::scFvPAX6 tg/o mice. PAX6 homeoprotein is reported to also have noncell autonomous activities (Di Lullo et al, 2011;Kaddour et al, 2019), and these mice showed no visual acuity loss. These results demonstrate that neutralizing extracellular OTX2 in the retina leads to decreased visual acuity at P30, but the present results do not allow us to determine whether this persists at later ages.…”

Section: Resultsmentioning

confidence: 97%

OTX2 Non-Cell Autonomous Activity Regulates Inner Retinal Function

Ibad

Mazhar

Vincent

et al. 2020

eNeuro

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OTX2 is a homeoprotein transcription factor expressed in photoreceptors and bipolar cells in the retina. OTX2, like many other homeoproteins, transfers between cells and exerts non-cell autonomous effects such as promoting the survival of retinal ganglion cells that do not express the protein. Here we used a genetic approach to target extracellular OTX2 in the retina by conditional expression of a secreted single-chain anti-OTX2 antibody. Compared with control mice, the expression of this antibody by parvalbumin-expressing neurons in the retina is followed by a reduction in visual acuity in 1-month-old mice with no alteration of the retinal structure or cell type number or aspect. The a-waves and b-waves measured by electroretinogram were also indistinguishable from those of control mice, suggesting no functional deficit of photoreceptors and bipolar cells. Mice expressing the OTX2-neutralizing antibody did show a significant doubling in the flicker amplitude and a reduction in oscillatory potential, consistent with a change in inner retinal function. Our results show that interfering in vivo with OTX2 non-cell autonomous activity in the postnatal retina leads to an alteration in inner retinal cell functions and causes a deficit in visual acuity.

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“…Similar to findings in PARP1 KOs ( Hong et al, 2019 ), McLoughlin et al (2012) reported that Dicer depletion reduces cell proliferation and increases apoptosis in the E15.5 cortex. Additionally, PARP1 has a number of known transcription factor targets that have been shown to regulate CR progenitor cell development and migration, including Ascl1/Mash1, Pax6, and Cxcl12 ( Stoykova et al, 2003 ; Ju et al, 2004 ; Borrell and Marín, 2006 ; Dixit et al, 2011 , p. 1; Yoo et al, 2011 ; Marković et al, 2013 ; Tolić et al, 2019 ; Kaddour et al, 2020 ). Further studies will be necessary to test the links between PARP1, transcription factor activity, miRNAs, and CR cell generation in the embryonic brain.…”

Section: Discussionmentioning

confidence: 99%

Poly (ADP-Ribose) Polymerase 1 Regulates Cajal–Retzius Cell Development and Neural Precursor Cell Adhesion

Nelson

Hoff

Zeese

et al. 2021

Front. Cell Dev. Biol.

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Poly (ADP-ribose) polymerase 1 (PARP1) is a ubiquitously expressed enzyme that regulates DNA damage repair, cell death, inflammation, and transcription. PARP1 functions by adding ADP-ribose polymers (PAR) to proteins including itself, using NAD+ as a donor. This post-translational modification known as PARylation results in changes in the activity of PARP1 and its substrate proteins and has been linked to the pathogenesis of various neurological diseases. PARP1 KO mice display schizophrenia-like behaviors, have impaired memory formation, and have defects in neuronal proliferation and survival, while mutations in genes that affect PARylation have been associated with intellectual disability, psychosis, neurodegeneration, and stroke in humans. Yet, the roles of PARP1 in brain development have not been extensively studied. We now find that loss of PARP1 leads to defects in brain development and increased neuronal density at birth. We further demonstrate that PARP1 loss increases the expression levels of genes associated with neuronal migration and adhesion in the E15.5 cerebral cortex, including Reln. This correlates with an increased number of Cajal–Retzius (CR) cells in vivo and in cultures of embryonic neural progenitor cells (NPCs) derived from the PARP1 KO cortex. Furthermore, PARP1 loss leads to increased NPC adhesion to N-cadherin, like that induced by experimental exposure to Reelin. Taken together, these results uncover a novel role for PARP1 in brain development, i.e., regulation of CR cells, neuronal density, and cell adhesion.

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Extracellular Pax6 Regulates Tangential Cajal–Retzius Cell Migration in the Developing Mouse Neocortex

Cited by 15 publications

References 31 publications

Homeoprotein transduction in neurodevelopment and physiopathology

Homeoprotein transduction in neurodevelopment and physiopathology

OTX2 Non-Cell Autonomous Activity Regulates Inner Retinal Function

Poly (ADP-Ribose) Polymerase 1 Regulates Cajal–Retzius Cell Development and Neural Precursor Cell Adhesion

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