visualization-thalamocortical-axon-branching-synapse-formation

Visualization of Thalamocortical Axon Branching and Synapse Formation in Organotypic Cocultures

Axon branching and synapse formation are crucial processes for establishing precise neuronal circuits. During development, sensory thalamocortical (TC) ...

Kanazawa University

Osaka University

Crystal structure of o-(p-N,N-dimethylaminobenzoyl)benzoic acid.

Crystal structure of 2-benzoyl-3,4,5,6-tetrachlorobenzoic acid.

To date there has been only 1 reported case of the symptom relapse of pediatric idiopathic intervertebral disk calcification (PIIDC), as described by Yoon and colleagues in 1987, who reported symptom relapse in a patient with multilevel PIIDC. Thus, symptom relapse in patients with single-level PIIDC have not been reported.

A pediatric case of single-level idiopathic cervical intervertebral disk calcification with symptom relapse 1 year after initial onset.

Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD.

Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.

Although it has been believed that the evolution of cortical folds was a milestone, allowing for an increase in the number of neurons in the cerebral cortex, the mechanisms underlying the formation of cortical folds are largely unknown. Here we show regional differences in the expression of fibroblast growth factor receptors (FGFRs) in the developing cerebral cortex of ferrets even before cortical folds are formed. By taking the advantage of ourelectroporation technique for ferrets, we found that cortical folding was impaired in the ferret cerebral cortex when FGF signaling was inhibited. We also found that FGF signaling was crucial for producing Pax6-positive neural progenitors in the outer subventricular zone (OSVZ) of the developing cerebral cortex. Furthermore, we found that upper layers of the cerebral cortex were preferentially reduced by inhibiting FGF signaling. Our results shed light on the mechanisms of cortical folding in gyrencephalic mammalian brains.

Gyrification of the cerebral cortex requires FGF signaling in the mammalian brain.

Leptomeningeal glioneuronal heterotopia (LGH) is a focal malformation of the cerebral cortex and frequently found in patients with thanatophoric dysplasia (TD). The pathophysiological mechanisms underlying LGH formation are still largely unclear because of difficulties in obtaining brain samples from human TD patients. Recently, we established a new animal model for analysing cortical malformations of human TD by utilizing our genetic manipulation technique for gyrencephalic carnivore ferrets. Here we investigated the pathophysiological mechanisms underlying the formation of LGH using our TD ferrets. We found that LGH was formed during corticogenesis in TD ferrets. Interestingly, we rarely found Ki-67-positive and phospho-histone H3-positive cells in LGH, suggesting that LGH formation does not involve cell proliferation. We uncovered that vimentin-positive radial glial fibers and doublecortin-positive migrating neurons were accumulated in LGH. This result may indicate that preferential cell migration into LGH underlies LGH formation. Our findings provide novel mechanistic insights into the pathogenesis of LGH in TD.

Article	Year
Crystal structure of o-(p-N,N-dimethylaminobenzoyl)benzoic acid. Analytical sciences : the international journal of the Japan Society for Analytical Chemistry\| PubMed ID: 11918204	2002
Crystal structure of 2-benzoyl-3,4,5,6-tetrachlorobenzoic acid. Analytical sciences : the international journal of the Japan Society for Analytical Chemistry\| PubMed ID: 12036138	2002
A pediatric case of single-level idiopathic cervical intervertebral disk calcification with symptom relapse 1 year after initial onset. Journal of pediatric orthopedics\| PubMed ID: 24096447	2014
Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals. Human molecular genetics\| PubMed ID: 28158406	2017
Gyrification of the cerebral cortex requires FGF signaling in the mammalian brain. eLife\| PubMed ID: 29132503	2017
Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic mammals. Human molecular genetics\| PubMed ID: 29325060	2018

Naoyuki Matsumoto

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