Neuronal generation, migration, and differentiation in the mouse hippocampal primoridium as revealed by enhanced green fluorescent protein gene transfer by means of in utero electroporation

Nakahira, Eiko; Yuasa, Shigeki

doi:10.1002/cne.20441

Cited by 105 publications

(98 citation statements)

References 64 publications

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“…5D). These findings revealed that the mutant CA1 neurons migrated more rapidly through the IZ to the CP than their wild-type counterparts, at a rate similar to transitional neocortex neurons (12). Therefore, the altered migratory behavior also supports the notion that the mutant CA1 neurons have acquired the identity of transitional neocortex neurons.…”

Section: Increased Apoptosis In the Postnatal Hippocampus Of Zbtb20 Nullsupporting

confidence: 57%

Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus

Xie¹,

Ma²,

Wyatt³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

110

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The development of hippocampal circuitry depends on the proper assembly of correctly specified and fully differentiated hippocampal neurons. Little is known about factors that control the hippocampal specification. Here, we show that zinc finger protein Zbtb20 is essential for the specification of hippocampal CA1 field identity. We found that Zbtb20 expression was initially activated in the hippocampal anlage at the onset of corticogenesis, and persisted in immature hippocampal neurons. Targeted deletion of Zbtb20 in mice did not compromise the progenitor proliferation in the hippocampal and adjacent transitional ventricular zone, but led to the transformation of the hippocampal CA1 field into a transitional neocortex-like structure, as evidenced by cytoarchitectural, neuronal migration, and gene expression phenotypes. Correspondingly, the subiculum was ectopically located adjacent to the CA3 in mutant. Although the field identities of the mutant CA3 and dentate gyrus (DG) were largely maintained, their projections were severely impaired. The hippocampus of Zbtb20 null mice was reduced in size, and exhibited increased apoptotic cell death during postnatal development. Our data establish an essential role of Zbtb20 in the specification of CA1 field identity by repressing adjacent transitional neocortex-specific fate determination.cell fate | neocortex | zinc finger transcription factor

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Section: Increased Apoptosis In the Postnatal Hippocampus Of Zbtb20 Nullsupporting

confidence: 57%

Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus

Xie¹,

Ma²,

Wyatt³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

110

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“…The Par complex may not be necessary for axon specification in these neurons because they are initially unipolar and extend only a single process (28,29). By contrast, hippocampal neurons display a multipolar morphology already during their migration from the ventricular zone (30).…”

Section: Discussionmentioning

confidence: 94%

The Interaction of mPar3 with the Ubiquitin Ligase Smurf2 Is Required for the Establishment of Neuronal Polarity

Schwamborn

Khazaei

Püschel

2007

Journal of Biological Chemistry

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The Par polarity complex consisting of the evolutionarily conserved proteins mPar3, mPar6, and aPKC regulates cell polarity in many cell types including neurons. Here we show that mPar3 is required for the establishment of neuronal polarity and links the Smurf2 to Kinesin-2. The HECT domain E3 ubiquitin ligase Smurf2 ensures that neurons extend only a single axon by initiating the degradation of inactive Rap1B through the ubiquitin/ proteasome system. Its interaction with mPar3 is required to localize Smurf2 to growth cones and restrict Rap1B to the axon. Interfering with the binding of mPar3 to Kinesin-2 or Smurf2 to mPar3 and knockdown of mPar3 by RNAi disrupt the establishment of neuronal polarity through the failure to restrict Rap1B to a single neurite.During the differentiation of hippocampal neurons, unpolarized cells initially form several equivalent neurites, all of which have the potential to become an axon (stage 2) (1). Neuronal polarity is established when one of these is selected as the axon (stage 3) by a signaling pathway that includes PI3K, 4 the GTPases Rap1B, Cdc42, and Rac, the Par polarity complex, and GSK3␤ (2-8). The Par complex consisting of mPar3, mPar6, and aPKCs (PKC and PKC) plays an essential role in determining polarity in many cell types (9). mPar3 promotes axon extension downstream of Cdc42 through the STEF-dependent activation of Rac and the stimulation of aPKC. mPar6 interacts specifically with GTP-bound Cdc42 and Rac1 (10, 11). Binding of Cdc42 enhances the activity of mPar6-associated aPKCs (11,12). In addition, mPar3 interacts with the Rac-specific guanine nucleotide-exchange factors (GEFs) STEF and Tiam1 to control tight junction assembly and to mediate the activation of Rac by Cdc42 through the Par complex to promote axon growth (5,13,14). In neurons, mPar3 and mPar6 are present in all processes of non-polarized stage 2 neurons and become restricted to the axon of polarized stage 3 neurons (6, 7). Overexpression of mPar3 or mPar6 disrupts neuronal polarity and induces the extension of several long but Tau-1 negative processes instead of a single axon (4, 7). The mPar3 C terminus interacts with the Kinesin-2 subunit KIF3A (4). This interaction is essential for the transport of mPar3 and aPKCs into neurites and the establishment of neuronal polarity.We have shown that the sequential activity of the GTPases Rap1B and Cdc42 directs the establishment of polarity in hippocampal neurons downstream of PI3K (6). Initially, Rap1B is present at the tips of all neurites of unpolarized stage 2 neurons but, concomitant with the appearance of mPar3 in all processes, is restricted to a single neurite before the axon becomes distinguishable, and the Par complex is localized exclusively to the axon (6, 7). Rap1B is necessary and sufficient to specify axonal identity. Therefore, the restriction of Rap1B to a single neurite is an essential step in the establishment of neuronal polarity. This restriction is mediated by the selective degradation of Rap1B by the UPS and prevents the formation of ...

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“…and F.M., unpublished). Given that immature DG neurons (Prox1 and NeuroD double positive) retain plasticity between the CA3 pyramidal and DG granule cell fates, Wnt signaling from the cortical hem may act as an instructive signal to sort the cell fates of postmitotic cells migrating toward the presumptive DG or CA3 (Nakahira and Yuasa, 2005).…”

Section: Specification Of Hippocampal Neuronal Identitymentioning

confidence: 99%

Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus

Iwano¹,

Masuda²,

et al. 2012

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The brain is composed of diverse types of neurons that fulfill distinct roles in neuronal circuits, as manifested by the hippocampus, where pyramidal neurons and granule cells constitute functionally distinct domains: cornu ammonis (CA) and dentate gyrus (DG), respectively. Little is known about how these two types of neuron differentiate during hippocampal development, although a set of transcription factors that is expressed in progenitor cells is known to be required for the survival of granule cells. Here, we demonstrate in mice that Prox1, a transcription factor constitutively expressed in the granule cell lineage, postmitotically functions to specify DG granule cell identity. Postmitotic elimination of Prox1 caused immature DG neurons to lose the granule cell identity and in turn terminally differentiate into the pyramidal cell type manifesting CA3 neuronal identity. By contrast, Prox1 overexpression caused opposing effects on presumptive hippocampal pyramidal cells. These results indicate that the immature DG cell has the potential to become a granule cell or a pyramidal cell, and Prox1 defines the granule cell identity. This bi-potency is lost in mature DG cells, although Prox1 is still required for correct gene expression in DG granule cells. Thus, our data indicate that Prox1 acts as a postmitotic cell fate determinant for DG granule cells over the CA3 pyramidal cell fate and is crucial for maintenance of the granule cell identity throughout the life.

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Neuronal generation, migration, and differentiation in the mouse hippocampal primoridium as revealed by enhanced green fluorescent protein gene transfer by means of in utero electroporation

Cited by 105 publications

References 64 publications

Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus

Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus

The Interaction of mPar3 with the Ubiquitin Ligase Smurf2 Is Required for the Establishment of Neuronal Polarity

Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus

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