Dendritic Anomalies in Disorders Associated with Mental Retardation

Kaufmann, Walter E.; Moser, Hugo W.

doi:10.1093/cercor/10.10.981

Cited by 681 publications

(498 citation statements)

References 107 publications

(129 reference statements)

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“…Similar results have been observed in the Ts65Dn mouse model (Takashima et al 1981(Takashima et al , 1989Kaufmann and Moser 2000;Dierssen et al 2003). The dendritic atrophy could be related to the increased inhibition observed in the patients and models of DS.…”

Section: Introductionsupporting

confidence: 84%

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

et al. 2010

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Down's syndrome (DS), with an incidence of one in 800 live births, is the most common genetic disorder associated with mental retardation. This trisomy on chromosome 21 induces a variable phenotype in which the only common feature is the presence of mental retardation. The neural mechanisms underlying mental retardation might include defects in the formation of neuronal networks and neural plasticity. DS patients have alterations in the morphology, the density and the distribution of dendritic spines in the pyramidal neurons of the cortex. Our hypothesis is that the deficits in dendritic arborization observed in the principal neurons of DS patients and Ts65Dn mice (a model for DS that mimics most of the structural alterations observed in humans) may be mediated to some extent by changes in their inhibitory inputs. Different types of interneurons control different types of inhibition. Therefore, to understand well the changes in inhibition in DS, it is necessary to study the different types of interneurons separately. We have studied the expression of synaptophysin, Glutamic acid decarboxylase-67 (GAD-67) and calcium-binding protein-expressing cells in the primary somatosensory cortex of 4-5 month old Ts65Dn mice. We have observed an increment of GAD67 immunoreactivity that is related mainly to an increment of calretinin-immunoreactive cells and among them the ones with bipolar morphology. Since there is a propensity for epilepsy in DS patients, this increase in interneurons might reflect an attempt by the system to block overexcitation rather than an increment in total inhibition and could explain the deficit in interneurons and principal cells observed in elderly DS patients.

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Section: Introductionsupporting

confidence: 84%

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

et al. 2010

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“…Underscoring the potential physiological significance of the maintenance of dendritic fields, dendrites of layer III cortical neurons develop normally but then degenerate postnatally in Down syndrome patients (Benavides-Piccione et al 2004). Furthermore, defects in dendrite development are the strongest correlate with mental retardation, and dendrite maintenance defects may underlie a variety of developmental disorders (Kaufmann and Moser 2000).…”

mentioning

confidence: 99%

Polycomb genes interact with the tumor suppressor genes hippo and warts in the maintenance of Drosophila sensory neuron dendrites

Parrish¹,

Emoto²,

Jan³

2007

Genes Dev.

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Dendritic fields are important determinants of neuronal function. However, how neurons establish and then maintain their dendritic fields is not well understood. Here we show that Polycomb group (PcG) genes are required for maintenance of complete and nonoverlapping dendritic coverage of the larval body wall by Drosophila class IV dendrite arborization (da) neurons. In esc, Su(z)12, or Pc mutants, dendritic fields are established normally, but class IV neurons display a gradual loss of dendritic coverage, while axons remain normal in appearance, demonstrating that PcG genes are specifically required for dendrite maintenance. Both multiprotein Polycomb repressor complexes (PRCs) involved in transcriptional silencing are implicated in regulation of dendrite arborization in class IV da neurons, likely through regulation of homeobox (Hox) transcription factors. We further show genetic interactions and association between PcG proteins and the tumor suppressor kinase Warts (Wts), providing evidence for their cooperation in multiple developmental processes including dendrite maintenance.[Keywords: Drosophila; neuron; dendrite; Polycomb; homeobox; tumor suppressor] Supplemental material is available at http://www.genesdev.org. Received November 20, 2006; revised version accepted February 26, 2007. Dendrite arborization patterns are important for neuronal function and proper wiring of neuronal circuitry. Moreover, sensory perception in some cases depends on complete and nonredundant coverage of the receptive field by dendrites of functionally related neurons, a phenomenon known as tiling. For example, many types of neurons tile the mammalian retina, most likely to ensure efficient and unambiguous representation of the visual field. At least 11 distinct physiological classes of rabbit retinal ganglion cells (RGCs) cover their receptive field nonredundantly by avoiding overlap between dendrites of a single neuron as well as between dendrites of the same type of neurons, whereas dendrites of different types of neurons freely cross one another (Wassle et al. 1978(Wassle et al. , 1983Rockhill et al. 2002). Similarly, >20 classes of amacrine cells in the rabbit retina can be distinguished on the basis of dendrite morphology, and many of these classes of amacrine cells appear to tile the retina. Sensory neurons in Manduca, Drosophila, and the leech Hirudu medicinalis also exhibit tiling, suggesting that tiling may be a general mechanism to organize dendritic fields Grueber and Jan 2004).Once neurons tile their receptive field and achieve complete coverage during development, the tiling is maintained even as the territory changes; for example, as the animal grows in size. Whereas like-repels-like homotypic repulsion is one mechanism important for the establishment of receptive fields (Grueber et al. 2003b), how tiling is maintained after the establishment of the dendritic field is not well understood. Underscoring the potential physiological significance of the maintenance of dendritic fields, dendrites of layer III cortical ...

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“…Properly arborized dendrites provide structural support for information processing within the nervous system, and dendritic abnormalities are often associated with cognitive diseases, such as mental retardation and autism [1]. Dendritic arborization and complexity is tightly controlled by a combination of extrinsic and intrinsic factors.…”

Section: Introductionmentioning

confidence: 99%

Serum inducible kinase is a positive regulator of cortical dendrite development and is required for BDNF-promoted dendritic arborization

Guo

Tan

et al. 2011

Cell Res

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Serum inducible kinase (SNK), also known as polo-like kinase 2 (PLK2), is a known regulator of mitosis, synaptogenesis and synaptic homeostasis. However, its role in early cortical development is unknown. Herein, we show that snk is expressed in the cortical plate from embryonic day 14, but not in the ventricular/subventricular zones (VZ/ SVZ), and SNK protein localizes to the soma and dendrites of cultured immature cortical neurons. Loss of SNK impaired dendritic but not axonal arborization in a dose-dependent manner and overexpression had opposite effects, both in vitro and in vivo. Overexpression of SNK also caused abnormal branching of the leading process of migrating cortical neurons in electroporated cortices. The kinase activity was necessary for these effects. Extracellular signalregulated kinase (ERK) pathway activity downstream of brain-derived neurotrophic factor (BDNF) stimulation led to increases in SNK protein expression via transcriptional regulation, and this upregulation was necessary for the growth-promoting effect of BDNF on dendritic arborization. Taken together, our results indicate that SNK is essential for dendrite morphogenesis in cortical neurons.

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Dendritic Anomalies in Disorders Associated with Mental Retardation

Cited by 681 publications

References 107 publications

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

Polycomb genes interact with the tumor suppressor genes hippo and warts in the maintenance of Drosophila sensory neuron dendrites

Serum inducible kinase is a positive regulator of cortical dendrite development and is required for BDNF-promoted dendritic arborization

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