Reelin is a positional signal for the lamination of dentate granule cells

Zhao, Shanting; Chai, Xuejun; Förster, Eckart; Frotscher, Michael

doi:10.1242/dev.01387

Cited by 121 publications

(116 citation statements)

References 37 publications

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“…Slice cultures were prepared from newborn [postnatal day 0 (P0)] or P5 homozygous Reeler mutant mice and wildtype or heterozygous littermates as described previously (Zhao et al, 2004). In brief, hippocampi were excised, cut in 400 m slices, and incubated as static cultures in 1 ml nutrition medium (25% heatinactivated horse serum, 25% Hank's balanced salt solution, 50% minimal essential medium, 2 mM glutamine, pH 7.2) at 5% CO 2 , 37°C (Stoppini et al, 1991).…”

Section: Methodsmentioning

confidence: 99%

“…The developmental defects in the Reeler hippocampus can be rescued in slice culture preparations by exogenous Reelin administration (Zhao et al, 2004). If Reelin regulates radial glia growth independently of Notch1 activity, rescue of fiber density by exogenous Reelin should be possible despite inhibition of ␥-secretase with DAPT.…”

Section: Inhibition Of Notch Activation Blocks Reelin-dependent Rescumentioning

confidence: 99%

“…An early exhaustion of radial glial cells potentially explains the decrease in postnatal neurogenesis in Reeler mutants (Zhao et al, 2007). Radial glial cells express the Reelin receptors ApoER2 (apolipoprotein E receptor 2) and VLDLR (very low density lipoprotein receptor) , and Reelin stimulates and directs radial glial fiber growth Hartfuss et al, 2003;Zhao et al, 2004Zhao et al, , 2006.…”

Section: Introductionmentioning

confidence: 99%

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Reelin and Notch1 Cooperate in the Development of the Dentate Gyrus

Sibbe¹,

Förster²,

Basak³

et al. 2009

Journal of Neuroscience

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The development of the hippocampal dentate gyrus is a complex process in which several signaling pathways are involved and likely interact with each other. The extracellular matrix molecule Reelin is necessary both for normal development of the dentate gyrus radial glia and neuronal migration. In Reelin-deficient Reeler mice, the hippocampal radial glial scaffold fails to form, and granule cells are dispersed throughout the dentate gyrus. Here, we show that both formation of the radial glia scaffold and lamination of the dentate gyrus depend on intact Notch signaling. Inhibition of Notch signaling in organotypic hippocampal slice cultures induced a phenotype reminiscent of the Reelin-deficient hippocampus, i.e., a reduced density of radial glia fibers and granule cell dispersion. Moreover, a Reelindependent rescue of the Reeler phenotype was blocked by inhibition of Notch activation. In the Reeler dentate gyrus, we found reduced Notch1 signaling; the activated Notch intracellular domain as well as the transcriptional targets, brain lipid-binding protein, and Hes5 are decreased. Disabled1, a component of the Reelin-signaling pathway colocalizes with Notch1, thus indicating a direct interaction between the Reelin-and Notch1-signaling pathways. These results suggest that Reelin enhances Notch1 signaling, thereby contributing to the formation of the radial glial scaffold and the normal development of the dentate gyrus.

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Section: Methodsmentioning

confidence: 99%

Section: Inhibition Of Notch Activation Blocks Reelin-dependent Rescumentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reelin and Notch1 Cooperate in the Development of the Dentate Gyrus

Sibbe¹,

Förster²,

Basak³

et al. 2009

Journal of Neuroscience

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“…These cells proliferate upon diverse functional and molecular stimuli, generate migratory neuroblasts as characterized by expression of doublecortin and PSA-NCAM (type D cells), and further differentiate into granule cells upon migration into the dentate gyrus Seri et al, 2004). Migratory guidance is provided by a scaffold of radial glial cells within the dentate gyrus (DG) as well as from reelin molecules secreted by Cajal-Retzius cells (Kim et al, 2002;Frotscher et al, 2003;Zhao et al, 2004). Newborn granule cells functionally integrate into the trisynaptic hippocampal pathway (van Praag et al, 2002;Ge et al, 2006;Ramirez-Amaya et al, 2006), expand dendrites into the molecular layer and axonal collaterals into the CA3 region (mossy fibers), where they form synaptic connections on large excrescences of pyramidal neurons within stratum lucidum (Hastings & Gould, 1999).…”

Section: Neurogenic Subregions In the Human Hippocampusmentioning

confidence: 99%

Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies

Siebzehnrubl

Blümcke

2008

Epilepsia

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SUMMARYAmple evidence points to the dentate gyrus as anatomical region for persistent neurogenesis in the adult mammalian brain. This has been confirmed in a variety of animal models under physiological as well as pathophysiological conditions. Notwithstanding, similar experiments are difficult to perform in humans. Postmortem studies demonstrated persisting neurogenesis in the elderly human brain. In addition, neural precursor cells can be isolated from surgical specimens obtained from patients with intractable temporal lobe epilepsy (TLE) and propagated or differentiated into neuronal and glial lineages. It remains a controversial issue, whether epileptic seizures have an effect on or even increase hippocampal neurogenesis in humans. Recent data support the notion that seizures induce neurogenesis in young patients, whereas the capacity of neuronal recruitment and proliferation decreases with age. Animal models of TLE further indicate that these newly generated neurons integrate into epileptogenic networks and contribute to increased seizure susceptibility. However, pathomorphological disturbances within the epileptic hippocampus, such as granule cell dispersion (GCD), may not directly result from compromised neurogenesis. Still, the majority of adult TLE patients present with significant dentate granule cell loss at an end stage of the disease, which relates to severe memory and learning disabilities. In conclusion, surgical specimens obtained from TLE patients represent an important tool to study mechanisms of stem cell recruitment, proliferation and differentiation in the human brain. In addition, increasing availability of surgical specimens opens new avenues to systematically explore disease pathomechanisms in chronic epilepsies.

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“…Transduction of reelin signaling occurs through interaction of disabled-1 (Dab1) with the intracellular NPxY motif of these receptors, resulting in tyrosine phosphorylation of Dab1, activation of the SFKs (Src family nonreceptor tyrosine kinases), and an ensuing signaling cascade that leads to proper neuronal migration (Howell et al, 1997(Howell et al, , 1999aTrommsdorff et al, 1998;Arnaud et al, 2003;Bock and Herz, 2003). Considering the fact that reelin is also abundantly expressed by interneurons, and all of the downstream signaling components exist in the postnatal hippocampus (Alcantara et al, 1998;Pesold et al, 1998;Abraham and Meyer, 2003;Zhao et al, 2004), it is intriguing to know whether reelinmediated signaling plays a physiological role in adult brain function.…”

Section: Introductionmentioning

confidence: 99%

Differential Reelin-Induced Enhancement of NMDA and AMPA Receptor Activity in the Adult Hippocampus

Qiu¹,

Zhao²,

Korwek³

et al. 2006

J. Neurosci.

166

161

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The developmental lamination of the hippocampus and other cortical structures requires a signaling cascade initiated by reelin and its receptors, apoER2 (apolipoprotein E receptor 2) and VLDLR (very-low-density lipoprotein receptor). However, the functional significance of continued reelin expression in the postnatal brain remains poorly understood. Here, we show that reelin application to adult mice hippocampal slices leads to enhanced glutamatergic transmission mediated by NMDA receptors (NMDARs) and AMPA receptors (AMPARs) through distinct mechanisms. Application of recombinant reelin enhanced NMDAR-mediated currents through postsynaptic mechanisms, as revealed by the variance-mean analysis of synaptic NMDAR currents, assessment of spontaneous miniature events, and the levels of NMDAR subunits at synaptic surface. In comparison, nonstationary fluctuation analysis of miniature AMPAR currents and quantification of synaptic surface proteins revealed that reelin-induced enhancement of AMPAR responses was mediated by increased AMPAR numbers. Reelin enhancement of synaptic NMDAR currents was abolished when receptor-associated protein (RAP) or the Src inhibitor 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1) was bath applied and was abrogated by includingPP1 in the recording electrodes. In comparison, including RAP or an inactive PP1 analog PP3 in the recording electrode was without effect. Interestingly, the increased AMPAR response after reelin application was not blocked by PP1 but was blocked by the phosphoinositide-3Ј kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride]. Furthermore, reelin-induced, PI3K-dependent AMPAR surface insertion was also observed in cultured hippocampal neurons. Together, these results reveal a differential functional coupling of reelin signaling with NMDAR and AMPAR function and define a novel mechanism for controlling synaptic strength and plasticity in the adult hippocampus.

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Reelin is a positional signal for the lamination of dentate granule cells

Cited by 121 publications

References 37 publications

Reelin and Notch1 Cooperate in the Development of the Dentate Gyrus

Reelin and Notch1 Cooperate in the Development of the Dentate Gyrus

Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies

Differential Reelin-Induced Enhancement of NMDA and AMPA Receptor Activity in the Adult Hippocampus

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