Genes and brain malformations associated with abnormal neuron positioning

Moffat, Jeffrey J.; Ka, Minhan; Jung, Eui‐Man; Kim, Woo Yang

doi:10.1186/s13041-015-0164-4

Cited by 69 publications

(53 citation statements)

References 164 publications

(177 reference statements)

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“…Disturbances in neuronal migration early in development are known to cause aberrant neuron positioning and synaptic connectivity, which in turn are linked to neurodevelopmental disorders in humans (Moffat et al., ). Our results in EtOH fish reveal marked disturbances from 24 to 28 hpf, showing alterations in the migration and direction of the bilateral hcrt neurons, including reduced displacement length, speed, and straightness and reduced migration in the dorsal and anterior directions.…”

Section: Discussionmentioning

confidence: 99%

Embryonic Ethanol Exposure Affects the Early Development, Migration, and Location of Hypocretin/Orexin Neurons in Zebrafish

Collier

Halkina

Min

et al. 2019

Alcoholism Clin & Exp Res

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Background: Embryonic ethanol (EtOH) exposure is known to increase alcohol drinking later in life and have long-term effects on neurochemical systems in the brain. With zebrafish having marked advantages for elucidating neural mechanisms underlying brain disorders, we recently tested and showed in these fish, similar to rodents, that low-dose embryonic EtOH stimulates voluntary consumption of EtOH while increasing expression of hypocretin/orexin (hcrt) neurons, a neuropeptide that promotes consummatory and reward-related behaviors. The goal of the present study was to characterize how embryonic EtOH affects early development of the hcrt system and produces persistent changes at older ages that may contribute to this increase in EtOH consumption.Methods: We utilized live imaging and Imaris software to investigate how low-dose embryonic EtOH (0.5%), administered from 22 to 24 hours postfertilization, affects specific properties of hcrt neurons in hcrt:EGFP transgenic zebrafish at different ages.Results: Time-lapse imaging from 24 to 28 hpf showed that embryonic EtOH increased the number of hcrt neurons, reduced the speed, straightness, and displacement of their migratory paths, and altered their direction early in development. At older ages up to 6 dpf, the embryonic EtOH-induced increase in hcrt neurons was persistent, and the neurons became more widely dispersed. These effects of embryonic EtOH were found to be asymmetric, occurring predominantly on the left side of the brain, and at 6 dpf, they resulted in marked changes in the anatomical location of the hcrt neurons, with some detected outside their normal position in the anterior hypothalamus again primarily on the left side.Conclusions: Our findings demonstrate that low-dose embryonic EtOH has diverse, persistent, and asymmetric effects on the early development of hypothalamic hcrt neurons, which lead to abnormalities in their ultimate location that may contribute to behavioral disturbances, including an increase in EtOH consumption.

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Section: Discussionmentioning

confidence: 99%

Embryonic Ethanol Exposure Affects the Early Development, Migration, and Location of Hypocretin/Orexin Neurons in Zebrafish

Collier

Halkina

Min

et al. 2019

Alcoholism Clin & Exp Res

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“…Significant changes in cell morphology, physiology, and synaptic connectivity also follow abnormal neuronal migration in the olfactory bulb [36], hippocampus [37], and pre-cerebellar nuclei [38]. Indeed, abnormal neuronal migration in humans is associated with a variety of neurological problems, such as seizures and cognitive impairment [39]. It seems likely that different strategies for synaptic specification are used in different contexts, depending on the nature of the circuits they are used to construct.…”

Section: Discussionmentioning

confidence: 99%

Key Features of Structural and Functional Organization of Zebrafish Facial Motor Neurons Are Resilient to Disruption of Neuronal Migration

McArthur

Fetcho

2017

Current Biology

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SUMMARY The location of neurons early in development can be critical for their ability to differentiate and receive normal synaptic inputs. Indeed, disruptions in neuronal positioning lead to a variety of neurological disorders. Neurons have, however, shifted their positions across phylogeny, suggesting that changes in location do not always spell functional disaster. To investigate the functional consequences of abnormal positioning, we leveraged previously reported genetic perturbations to disrupt normal neuronal migration – and thus positioning – in a population of cranial motor neurons, the facial branchiomotor neurons (FBMNs). We used a combination of topographical, morphological, physiological, and behavioral analyses to determine if key functional features of FBMNs were still established in migration mutants, in spite of a dramatic rostrocaudal re-positioning of these neurons in hindbrain. We discovered that FBMNs seem remarkably resilient to a disruption in positioning, suggesting that they may not rely heavily on rostrocaudal positioning to guide their functional development. Thus, the role of positioning may vary across the developing nervous system, with some populations – like facial motor neurons – exhibiting greater resilience to abnormal positioning that permits them to shift location as a part of evolutionary change.

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“…Defects in neuronal migration are the cause of disorders including lissencephaly, heterotopia, and focal cortical dysplasia that are associated with epileptic syndromes . In addition, granule cell dispersion is a frequently observed pathologic feature of HS‐TLE and is most likely caused by local deficiencies in the extracellular matrix protein reelin, which regulates neuronal migration .…”

Section: Suspected Mirna Involvement In Cellular Migration During Epimentioning

confidence: 99%

Involvement of microRNAs in epileptogenesis

Cattani

Allène²,

Seifert

et al. 2016

Epilepsia

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SUMMARYPatients who have sustained brain injury or had developmental brain lesions present a non-negligible risk for developing delayed epilepsy. Finding therapeutic strategies to prevent development of epilepsy in at-risk patients represents a crucial medical challenge. Noncoding microRNA molecules (miRNAs) are promising candidates in this area. Indeed, deregulation of diverse brain-specific miRNAs has been observed in animal models of epilepsy as well as in patients with epilepsy, mostly in temporal lobe epilepsy (TLE). Herein we review deregulated miRNAs reported in epilepsy with potential roles in key molecular and cellular processes underlying epileptogenesis, namely neuroinflammation, cell proliferation and differentiation, migration, apoptosis, and synaptic remodeling. We provide an up-to-date listing of miRNAs altered in epileptogenesis and assess recent functional studies that have interrogated their role in epilepsy. Last, we discuss potential applications of these findings for the future development of disease-modifying therapeutic strategies for antiepileptogenesis.

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Genes and brain malformations associated with abnormal neuron positioning

Cited by 69 publications

References 164 publications

Embryonic Ethanol Exposure Affects the Early Development, Migration, and Location of Hypocretin/Orexin Neurons in Zebrafish

Embryonic Ethanol Exposure Affects the Early Development, Migration, and Location of Hypocretin/Orexin Neurons in Zebrafish

Key Features of Structural and Functional Organization of Zebrafish Facial Motor Neurons Are Resilient to Disruption of Neuronal Migration

Involvement of microRNAs in epileptogenesis

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