Concise Review: Pax6 Transcription Factor Contributes to both Embryonic and Adult Neurogenesis as a Multifunctional Regulator

Osumi, Noriko; Shinohara, Hiroshi; Numayama-Tsuruta, Keiko; Maekawa, Motoko

doi:10.1634/stemcells.2007-0884

Cited by 312 publications

(300 citation statements)

References 139 publications

(167 reference statements)

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“…In the mouse embryo, Pax6 is expressed in the neuroectoderm of the FB and hindbrain [64]. In human stem cells PAX6 acts as a determinant of neuroectoderm fate [65][66][67]. Consistently, some expression was detected in hVMl cells, but it was higher in hNSl cells (Fig.…”

Section: Regionalization and Activation Of Developmental Gene Cascadementioning

confidence: 54%

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Seiz

Ramos-Gómez

Courtois

et al. 2012

Experimental Cell Research

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Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVMl model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and prodopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-X L induces an increase in the expression of key developmental genes (MSX1, Abbreviations: A9-DAn, (dopaminergic neuron from the A9 group); 6-OHDA, (6-hidroxydopamine); DA, (dopamine); DAn, (dopaminergic neuron); FB, (forebrain); FP, (floor plate); hESC, (human Embryonic stem cells); hNSC, (human neural stem cells); hVM, (human ventral mesencephalon); SNpc, (substantia nigra pars compacta); TH, (tyrosine hydroxylase); VM, (ventral mesencephalon); VM DAn, (dopaminergic neuron from ventral mesencephalon); VM hNSC, (human neural stem cells from ventral mesencephalon) NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (ENl, LMXIB, NURRl and PITX3). As a result, Bcl-X L anticipates and enhances DAn generation.

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Section: Regionalization and Activation Of Developmental Gene Cascadementioning

confidence: 54%

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Seiz

Ramos-Gómez

Courtois

et al. 2012

Experimental Cell Research

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“…CB 1 receptor signalling converges onto the activation of STAT3, a transcription factor responsible for gene expression regulation that is involved in cannabinoid-induced neurite outgrowth and ERK activation [76]. In neuroblastoma cells, CB 1 receptor-induced STAT3 activation relies on PI3K-dependent activation of the transcription factor Pax6 [81], a paired box family member essential for the generation of glutamatergic neurons and cortical neurogenesis [82]. In addition, CB 1 receptor prevents the inhibitory effect of breast cancer resistance associated on neuritogenesis [81].…”

Section: The Cb 1 Cannabinoid Receptor and Neural Differentiationmentioning

confidence: 99%

Endocannabinoids via CB₁receptors act as neurogenic niche cues during cortical development

Díaz-Alonso

Guzmán

Galve‐Roperh

2012

Phil. Trans. R. Soc. B

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During brain development, neurogenesis is precisely regulated by the concerted action of intrinsic factors and extracellular signalling systems that provide the necessary niche information to proliferating and differentiating cells. A number of recent studies have revealed a previously unknown role for the endocannabinoid (ECB) system in the control of embryonic neuronal development and maturation. Thus, the CB 1 cannabinoid receptor in concert with locally produced ECBs regulates neural progenitor (NP) proliferation, pyramidal specification and axonal navigation. In addition, subcellularly restricted ECB production acts as an axonal growth cone signal to regulate interneuron morphogenesis. These findings provide the rationale for understanding better the consequences of prenatal cannabinoid exposure, and emphasize a novel role of ECBs as neurogenic instructive cues involved in cortical development. In this review the implications of altered CB 1 -receptor-mediated signalling in developmental disorders and particularly in epileptogenesis are briefly discussed.

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“…This activity might be mediated by upregulation of Hes1 (Supporting Information Fig. S11) and downregulation of Pax6 and Tbr2, two well-established promoters of neuronogenesis progression [66] both frankly upregulated in Emx2 À/À brains (Supporting Information Fig. S12).…”

Section: Emx2 Channels Neural Precursors To Neuronal Differentiationmentioning

confidence: 99%

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

et al. 2010

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Neural stem cells (NSCs) give rise to all cell types forming the cortex: neurons, astrocytes, and oligodendrocytes. The transition from the former to the latter ones takes place via lineage-restricted progenitors in a highly regulated way. This process is mastered by large sets of genes, among which some implicated in central nervous system pattern formation. The aim of this study was to disentangle the kinetic and histogenetic roles exerted by two of these genes, Emx2 and Foxg1, in cortico-cerebral precursors. For this purpose, we set up a new integrated in vitro assay design. Embryonic cortical progenitors were transduced with lentiviral vectors driving overexpression of Emx2 and Foxg1 in NSCs and neuronal progenitors. Cells belonging to different neuronogenic and gliogenic compartments were labeled by spectrally distinguishable fluoroproteins driven by cell type-specific promoters and by cell type-specific antibodies and were scored via multiplex cytofluorometry and immunocytofluorescence. A detailed picture of Emx2 and Foxg1 activities in cortico-cerebral histogenesis resulted from this study. Unexpectedly, we found that both genes inhibit gliogenesis and promote neuronogenesis, through distinct mechanisms, and Foxg1 also dramatically stimulates neurite outgrowth. Remarkably, such activities, alone or combined, may be exploited to ameliorate the neuronal output obtainable from neural cultures, for purposes of cell-based brain repair. STEM CELLS

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Concise Review: Pax6 Transcription Factor Contributes to both Embryonic and Adult Neurogenesis as a Multifunctional Regulator

Cited by 312 publications

References 139 publications

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Endocannabinoids via CB₁receptors act as neurogenic niche cues during cortical development

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

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Concise Review: Pax6 Transcription Factor Contributes to both Embryonic and Adult Neurogenesis as a Multifunctional Regulator

Cited by 312 publications

References 139 publications

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Endocannabinoids via CB1receptors act as neurogenic niche cues during cortical development

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

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Endocannabinoids via CB₁receptors act as neurogenic niche cues during cortical development