Cortical Excitatory Neurons and Glia, But Not GABAergic Neurons, Are Produced in the Emx1-Expressing Lineage

Gorski, Jessica A.; Talley, Tiffany; Qiu, Mengsheng; Puelles, Luis; Rubenstein, John L.R.; Jones, Kathryn

doi:10.1523/jneurosci.22-15-06309.2002

Cited by 1,248 publications

(1,545 citation statements)

References 33 publications

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“…We next investigated the mechanism of Itgb1 action by detecting levels or states of neuronal polarity-associated proteins in Itgb1 cKO mice (Itgb1 f/f ; Emx1-Cre), which restricted Itgb1 deletion in dorsal telencephalic progenitors [37,38]. First, we determined the state of integrin-linked kinase (ILK), which has been shown to be involved in axon development of cultured hippocampal neurons [49].…”

Section: Itgb1 Regulation Of Neuronal Polarity Proteinsmentioning

confidence: 99%

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

et al. 2012

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Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron, but how this increased microtubule stability is achieved is unclear. Here, we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through β1 integrin (Itgb1). Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices. Active Itgb1 was found to be concentrated in laminin-contacting neurites. Axon formation was promoted and abolished by enhancing and attenuating Itgb1 signaling, respectively. Interestingly, laminin contact promoted plus-end microtubule assembly in a manner that required Itgb1. Moreover, stabilizing microtubules partially prevented polarization defects caused by Itgb1 downregulation. Finally, genetic ablation of Itgb1 in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons. Thus, laminin/Itgb1 signaling plays an instructive role in axon initiation and growth, both in vitro and in vivo, through the regulation of microtubule assembly. This study has established a linkage between an extrinsic factor and intrinsic cytoskeletal dynamics during neuronal polarization.

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Section: Itgb1 Regulation Of Neuronal Polarity Proteinsmentioning

confidence: 99%

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

et al. 2012

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“…It should be noted here that the Emx1-cre line, which also has a single copy of the cre gene, exhibits no overt cerebral cortical phenotype [ (Gorski et al, 2002) and Judson, Eagleson and Levitt, unpublished observations], even though it is maintained on the identical C57BL/6 background as the one used here (Table 2). An important difference between the two lines is the presence of a nuclear localization signal in the Foxg1-cre line (Hebert and McConnell, 2000), which is absent in the Emx1-cre line (Gorski et al, 2002), likely resulting in higher levels of Cre recombinase in the nucleus.…”

Section: Effects Of Cre Recombinasementioning

confidence: 99%

“…An important difference between the two lines is the presence of a nuclear localization signal in the Foxg1-cre line (Hebert and McConnell, 2000), which is absent in the Emx1-cre line (Gorski et al, 2002), likely resulting in higher levels of Cre recombinase in the nucleus. As noted above, there is evidence in vivo and in vitro that the accumulation of Cre recombinase specifically in the nucleus, rather than the absolute levels in the cell, underlies the DNA damage and growth inhibition observed in the absence of exogenous loxP sites (Baba et al, 2005, Forni et al, 2006.…”

Section: Effects Of Cre Recombinasementioning

confidence: 99%

Disruption of Foxg1 expression by knock-in of Cre recombinase: Effects on the development of the mouse telencephalon

et al. 2007

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The Cre/loxP system is used routinely to manipulate gene expression in the mouse nervous system. In order to delete genes specifically from the telencephalon, the Foxg1-cre line was created previously by replacing the intron-less Foxg1 coding region with cre, resulting in a Foxg1 heterozygous mouse. As the telencephalon of heterozygous Foxg1 mice was reported to be normal, this genotype often has been used as the control in subsequent analyses. Here we describe substantial disruption of forebrain development of heterozygous mice in the Foxg1-cre line, maintained on the C57BL/6J background. High resolution magnetic resonance microscopy reveals a significant reduction in the volume of the neocortex, hippocampus and striatum. The alteration in the neocortex results, in part, from a decrease in its tangential dimension, although gross patterning of the cortical sheet appears normal. This decrease is observed in three different Foxg1 heterozygous mouse lines, independent of the method of achieving deletion of the Foxg1 gene. Although Foxg1 is not expressed in the diencephalon, three-dimensional magnetic resonance microscopy revealed that thalamic volume in the adult is reduced. In contrast, at postnatal day 4, thalamic volume is normal, suggesting that interactions between cortex and dorsal thalamus postnatally produce the final adult thalamic phenotype. In the Foxg1-cre line maintained on the C57BL/6J background, the radial domain of the cerebral cortex also is disrupted substantially, particularly in supragranular layers. However, neither Foxg1 heterozygous mice of the Foxg1-tet line, nor those of the Foxg1-lacZ and Foxg1-cre lines maintained on a mixed background, displayed a reduced cortical thickness. Thus Cre recombinase contributes to the radial phenotype, although only in the context of the congenic C57BL/6J background. These observations highlight an important role for Foxg1 in cortical development, reveal noteworthy complexity in the invocation of specific mechanisms underlying phenotypes expressed following genetic manipulations and stress the importance of including appropriate controls of all genotypes. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Development of the cerebral cortex relies on extracellular cues and intrinsic signals that instruct the proliferation, differentiation and migration of neuronal precursors. The duration and location of these cues are critical to producing the final cortical architecture (FukuchiShimogori and Grove, 2001, Parnavelas et al., 2002, Rakic, 2002, Shimogori et al., 2004, Rash and Grove, 2006, Storm et al., 2006. The...

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“…Cortico-cerebral histogenesis is an extremely complex process, characterized by a well-defined spatial [1][2][3][4][5], temporal [6], and histogenetic plan [7]. Precursors giving rise to mature cell types include neural stem cells (NSCs), able to self-renew indefinitely and to generate all the mature cell types; and NSC-derived, lineage-restricted progenitors, characterized by more limited self-renewal potentials and more restricted histogenetic potencies.…”

Section: Introductionmentioning

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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Cortical Excitatory Neurons and Glia, But Not GABAergic Neurons, Are Produced in the Emx1-Expressing Lineage

Cited by 1,248 publications

References 33 publications

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

Disruption of Foxg1 expression by knock-in of Cre recombinase: Effects on the development of the mouse telencephalon

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

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