TBC1d24-ephrinB2 interaction regulates contact inhibition of locomotion in neural crest cell migration

Yoon, Jaeho; Hwang, Yoo-Seok; Lee, Moon-Sup; Sun, Jian; Cho, Hee Jun; Knapik, Laura; Daar, Ira

doi:10.1038/s41467-018-05924-9

Cited by 35 publications

(46 citation statements)

References 74 publications

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“…The cranial neural crest of Xenopus and zebrafish embryos migrates collectively in response to chemoattractants, such as SDF1 (Shellard and Mayor, 2016;Theveneau et al, 2010), by polarising at the level of the entire cluster. Supracellular polarity is imposed through CIL (Carmona-Fontaine et al, 2008;Yoon et al, 2018), the phenomenon of pairs of colliding cells repolarising and move awaying from each other (Roycroft and Mayor, 2016;Stramer and Mayor, 2017). In a cluster of high cell density, CIL causes outward protrusions to be formed at the free edge, but not internally, thereby contributing to the polarity of the entire cluster (Carmona-Fontaine et al, 2008).…”

Section: Supracellular Migrationmentioning

confidence: 99%

Supracellular migration – beyond collective cell migration

Shellard

Mayor

2019

Journal of Cell Science

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Collective cell migration is a highly complex process in which groups of cells move together. A fundamental question is how cell ensembles can migrate efficiently. In some cases, the group is no more than a collection of individual cells. In others, the group behaves as a supracellular unit, whereby the cell group could be considered as a giant 'supracell', the concept of which was conceived over a century ago. The development of recent tools has provided considerable evidence that cell collectives are highly cooperative, and their migration can better be understood at the tissue level, rather than at the cell level. In this Review, we will define supracellular migration as a type of collective cell migration that operates at a scale higher than the individual cells. We will discuss key concepts of supracellular migration, review recent evidence of collectives exhibiting supracellular features and argue that many seemingly complex collective movements could be better explained by considering the participating cells as supracellular entities.

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Section: Supracellular Migrationmentioning

confidence: 99%

Supracellular migration – beyond collective cell migration

Shellard

Mayor

2019

Journal of Cell Science

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“…ARF6 (ADP-ribosylation factor) is a small GTPase crucial for membrane trafficking (10,22) that binds TBC1D24, which may modulate ARF6 activation that regulates vesicle trafficking (10,22). In Xenopus laevis, TBC1D24 interacts indirectly with ephrinB2 through Dishevelled and is important for cranial neural crest migration (23). Additionally, mutations of Sky, the Drosophila melanogaster ortholog of mammalian TBC1D24, result in severe brain lesions and seizure-like behavior due to deficits of presynaptic trafficking of vesicles (2,17).…”

Section: Introductionmentioning

confidence: 99%

The phenotypic landscape of a Tbc1d24 mutant mouse includes convulsive seizures resembling human early infantile epileptic encephalopathy

Tona

Chen

Nakano

et al. 2019

Human Molecular Genetics

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Epilepsy, deafness, onychodystrophy, osteodystrophy and intellectual disability are associated with a spectrum of mutations of human TBC1D24. The mechanisms underlying TBC1D24-associated disorders and the functions of TBC1D24 are not well understood. Using CRISPR-Cas9 genome editing, we engineered a mouse with a premature translation stop codon equivalent to human S324Tfs * 3, a recessive mutation of TBC1D24 associated with early infantile epileptic encephalopathy (EIEE). Homozygous S324Tfs * 3 mice have normal auditory and vestibular functions but show an abrupt onset of spontaneous seizures at postnatal day 15 recapitulating human EIEE. The S324Tfs * 3 variant is located in an alternatively spliced micro-exon encoding six perfectly conserved amino acids incorporated postnatally into TBC1D24 protein due to a micro-exon utilization switch. During embryonic and early postnatal development, S324Tfs * 3 homozygotes produce predominantly the shorter wild-type TBC1D24 protein isoform that omits the micro-exon. S324Tfs * 3 homozygotes show an abrupt onset of seizures at P15 that correlates with a developmental switch to utilization of the micro-exon. A mouse deficient for alternative splice factor SRRM3 impairs incorporation of the Tbc1d24 micro-exon. Wild-type Tbc1d24 mRNA is abundantly expressed in the hippocampus using RNAscope in situ hybridization. Immunogold electron microscopy using a TBC1D24-specific antibody revealed that TBC1D24 is associated with clathrin-coated vesicles and synapses of hippocampal neurons, suggesting a crucial role of TBC1D24 in vesicle trafficking important for neuronal signal transmission. This is the first characterization of a mouse model of human TBC1D24-associated EIEE that can now be used to screen for antiepileptogenic drugs ameliorating TBCID24 seizure disorders.

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“…Perhaps the pleiotropy, associated with different variants of TBC1D24, results from a composite of disabled binding motifs for an array of interacting protein partners of TBC1D24. To date, the reported binding partners of TBC1D24 include ARF6 (ADP-ribosylation factor) [ 53 , 54 ] and ephrinB2 [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Mouse Models of Human Pathogenic Variants of TBC1D24 Associated with Non-Syndromic Deafness DFNB86 and DFNA65 and Syndromes Involving Deafness

Tona

López

Fenollar–Ferrer

et al. 2020

Genes

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Human pathogenic variants of TBC1D24 are associated with clinically heterogeneous phenotypes, including recessive nonsyndromic deafness DFNB86, dominant nonsyndromic deafness DFNA65, seizure accompanied by deafness, a variety of isolated seizure phenotypes and DOORS syndrome, characterized by deafness, onychodystrophy, osteodystrophy, intellectual disability and seizures. Thirty-five pathogenic variants of human TBC1D24 associated with deafness have been reported. However, functions of TBC1D24 in the inner ear and the pathophysiology of TBC1D24-related deafness are unknown. In this study, a novel splice-site variant of TBC1D24 c.965 + 1G > A in compound heterozygosity with c.641G > A p.(Arg214His) was found to be segregating in a Pakistani family. Affected individuals exhibited, either a deafness-seizure syndrome or nonsyndromic deafness. In human temporal bones, TBC1D24 immunolocalized in hair cells and spiral ganglion neurons, whereas in mouse cochlea, Tbc1d24 expression was detected only in spiral ganglion neurons. We engineered mouse models of DFNB86 p.(Asp70Tyr) and DFNA65 p.(Ser178Leu) nonsyndromic deafness and syndromic forms of deafness p.(His336Glnfs*12) that have the same pathogenic variants that were reported for human TBC1D24. Unexpectedly, no auditory dysfunction was detected in Tbc1d24 mutant mice, although homozygosity for some of the variants caused seizures or lethality. We provide some insightful supporting data to explain the phenotypic differences resulting from equivalent pathogenic variants of mouse Tbc1d24 and human TBC1D24.

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TBC1d24-ephrinB2 interaction regulates contact inhibition of locomotion in neural crest cell migration

Cited by 35 publications

References 74 publications

Supracellular migration – beyond collective cell migration

Supracellular migration – beyond collective cell migration

The phenotypic landscape of a Tbc1d24 mutant mouse includes convulsive seizures resembling human early infantile epileptic encephalopathy

Mouse Models of Human Pathogenic Variants of TBC1D24 Associated with Non-Syndromic Deafness DFNB86 and DFNA65 and Syndromes Involving Deafness

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