Axon Guidance Mechanisms for Establishment of Callosal Connections

Nishikimi, Mitsuaki; Oishi, Koji; Nakajima, Kazunori

doi:10.1155/2013/149060

Cited by 31 publications

(21 citation statements)

References 77 publications

(88 reference statements)

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“…The observed reductions in interhemispheric connectivity in bipolar I disorder patients are consistent with previous reports of reduced integrity of the CC in bipolar disorder [Barysheva et al, 2013;Emsell et al, 2013;Lagopoulos et al, 2013;Leow et al, 2013;Sarrazin et al, 2014;Torgerson et al, 2013;Wang et al, 2008] and may be reflective of a decrease in the number, density, caliber, and/or myelination of callosal axons, with recent findings pointing more towards myelination than axon abnormalities [Lewandowski et al, 2014]. Around 200-250 million axons pass through the CC [Nishikimi et al, 2013;Paul et al, 2007] to connect primary, secondary, and higher-order cortices [Aboitiz et al, 2003]. Interhemispheric axons have widespread arbors that terminate in many regions besides the topographically equivalent one [Houzel and Milleret, 1999] and it has been suggested that these heterotopic projections may be important to propagate activity to other areas, thereby contributing to the formation of large-scale neuronal ensembles promoting diverse aspects of cortical processing [Varela et al, 2001].…”

Section: Discussionsupporting

confidence: 89%

Brain network analysis reveals affected connectome structure in bipolar I disorder

et al. 2015

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The notion of healthy brain function emerging from coordinated neural activity constrained by the brain’s network of anatomical connections – i.e. the connectome – suggests that alterations in the connectome’s wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs and affected ‘rich club’ organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, inter-hemispheric connections) of the brain’s network. We find that bipolar I disorder patients exhibit reduced global efficiency (−4.4%, p = 0.002) and that this deficit relates (r = 0.56, p < 0.001) to reduced connectivity strength of inter-hemispheric connections (−13.0%, p = 0.001). Bipolar disorder patients were found not to show predominant alterations in the strength of brain hub connections in general, or of connections spanning brain hubs (i.e., ‘rich club’ connections) in particular (all p > 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency related to disruptions in inter-hemispheric connectivity, while the central ‘rich club’ system appears not to be particularly affected.

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Section: Discussionsupporting

confidence: 89%

Brain network analysis reveals affected connectome structure in bipolar I disorder

et al. 2015

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“…MicroRNA was recently discovered to serve as another level of regulators for these chemical cues and related signalling pathways (Chiu et al, 2014; Iyer et al., 2014). Axon guidance crossing CNS midline in developing spinal cord, the cortico-spinal tract (CST) and the corpus callosum is guided mainly by short-range cues derived from the midline structure and the neighbouring pioneer axons (Kaprielian et al, 2000; Nishikimi et al, 2013). …”

Section: Synaptogenesis and Neural Circuit Developmentmentioning

confidence: 99%

Cellular and molecular introduction to brain development

Jiang

Nardelli

2016

Neurobiology of Disease

138

118

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Advances in the study of brain development over the last decades, especially recent findings regarding the evolutionary expansion of the human neocortex, and large-scale analyses of the proteome/transcriptome in the human brain, have offered novel insights into the molecular mechanisms guiding neural maturation, and the pathophysiology of multiple forms of neurological disorders. As a preamble to reviews of this issue, we provide an overview of the cellular, molecular and genetic bases of brain development with an emphasis on the major mechanisms associated with landmarks of normal neural development in the embryonic stage and early postnatal life, including neural stem/progenitor cell proliferation, cortical neuronal migration, evolution and folding of the cerebral cortex, synaptogenesis and neural circuit development, gliogenesis and myelination. We will only briefly depict developmental disorders that result from perturbations of these cellular or molecular mechanisms, and the most common perinatal brain injuries that could disturb normal brain development.

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“…Callosal formation requires a cascade of dynamic events to be precisely coordinated spatially and temporally (Donahoo and Richards, 2009;Fame et al, 2011;Nishikimi et al, 2013). Callosal projection neurons mainly reside in cortical layers II and III and, to a lesser extent, layers V and VI.…”

Section: Introductionmentioning

confidence: 99%

The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap

Lavado¹,

Ware²,

Paré³

et al. 2014

Journal of Cell Science

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The corpus callosum connects cerebral hemispheres and is the largest axon tract in the mammalian brain. Callosal malformations are among the most common congenital brain anomalies and are associated with a wide range of neuropsychological deficits. Crossing of the midline by callosal axons relies on a proper midline environment that harbors guidepost cells emitting guidance cues to instruct callosal axon navigation. Little is known about what controls the formation of the midline environment. We find that two components of the Hippo pathway, the tumor suppressor Nf2 (Merlin) and the transcriptional coactivator Yap (Yap1), regulate guidepost development and expression of the guidance cue Slit2 in mouse. During normal brain development, Nf2 suppresses Yap activity in neural progenitor cells to promote guidepost cell differentiation and prevent ectopic Slit2 expression. Loss of Nf2 causes malformation of midline guideposts and Slit2 upregulation, resulting in callosal agenesis. Slit2 heterozygosity and Yap deletion both restore callosal formation in Nf2 mutants. Furthermore, selectively elevating Yap activity in midline neural progenitors is sufficient to disrupt guidepost formation, upregulate Slit2 and prevent midline crossing. The Hippo pathway is known for its role in controlling organ growth and tumorigenesis. Our study identifies a novel role of this pathway in axon guidance. Moreover, by linking axon pathfinding and neural progenitor behaviors, our results provide an example of the intricate coordination between growth and wiring during brain development.

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Axon Guidance Mechanisms for Establishment of Callosal Connections

Cited by 31 publications

References 77 publications

Brain network analysis reveals affected connectome structure in bipolar I disorder

Brain network analysis reveals affected connectome structure in bipolar I disorder

Cellular and molecular introduction to brain development

The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap

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