Biology subjects

Takenoshita, Y.

Publications and source records attributed to Takenoshita, Y..

4 recordsLinked to original sources

bioRxiv2026

Non-invasive genomic sampling uncovers novel connectivities and origins of confiscated gorillas

BackgroundGorillas are a group of African great apes with two species and four subspecies that are currently critically endangered or endangered. Previous studies that analysed the genetics of wild gorillas from non-invasive samples, such as faeces or hair, analysed short mitochondrial or nuclear markers, which may not reflect the wider nuclear genome. Recent technical advances in target capture hybridisation, enrich the endogenous DNA content of non-invasive samples, allowing contiguous genomic regions to be sequenced. ResultsHere, we generated georeferenced genetic data from faecal and hair samples of 280 wild gorillas, sampled from three of the four gorilla subspecies, across large parts of their present-day distributions. With this expanded representation of gorilla genetic diversity in the wild, we detected three population clusters in western lowland gorillas, with the Sangha River and its affluents acting as significant barriers to gene flow. We reconstructed patterns of past population connectivity between western lowland gorillas in the north-eastern distribution range and Cross River gorillas, which may have been facilitated by a migration corridor also used by the Central and Nigeria-Cameroon chimpanzee subspecies. Finally, we predicted the geographic origins of wild-born gorillas, achieving a mean prediction error of 65 km, with a population-level resolution for mountain gorillas and some populations of western lowland gorillas. ConclusionOur work characterises fine-scale population structure in western lowland gorillas, which will be informative for future conservation strategies. This proof of concept in predicting geographic locations of wild gorillas, will be useful for future applications to geolocalise trafficked or rescued gorillas.

evolutionary biology↗

bioRxiv2025

Functional genetics with a hypomorphic CENP-C mutant reveals a regulatory system for chromosome congression

Chromosome congression is a key process that acts to align chromosomes at the spindle equator via kinetochore-microtubule interactions, with defects in chromosome alignment leading to chromosomal instability. However, defining the mechanisms that underlie chromosome congression is limited due to the multiple factors that act in parallel to regulate chromosome movement. Here, we conducted a genome-wide Cas9-based functional genetics screen using a hypomorphic CENP-C mutant that affects its kinetochore interactions. Our analysis identified KIF18A, whose knockout resulted in synthetic lethality with the CENP-C mutant. Further analysis revealed that the synthetic defect was due to a reduction in CENP-E function in the CENP-C mutant. Our work suggests that KIF18A promotes chromosome alignment in cooperation with CENP-E downstream of CENP-C during early prometaphase. Thus, our analysis enables us to dissect parallel molecular mechanisms for chromosome congression and identify sensitivities and biomarkers that might guide anti-KIF18A chemotherapeutics.

cell biology↗

bioRxiv2024

Molecular details and phospho-regulation of the CENP-T-Mis12 complex interaction during mitosis in DT40 cells

To establish bi-polar attachments of microtubules to sister chromatids, an inner kinetochore subcomplex, the constitutive centromere-associated network (CCAN), is assembled on centromeric chromatin and recruits the microtubule-binding subcomplex called the KMN network. Although it is important to characterize the interaction between CCAN and KMN, it is difficult to evaluate the significance of each interaction in cells, since CCAN proteins CENP-C and CENP-T independently bind to the Mis12 complex (Mis12C) of KMN. Here, we demonstrate molecular details of the CENP-T-Mis12C interaction using chicken DT40 cells lacking CENP-C-Mis12C interaction. Based on AlphaFold2 predictions, we identified two binding surfaces for the CENP-T-Mis12C interaction, demonstrating that each surface is critical for Mis12C recruitment and cell viability. This interaction via two interaction surfaces is cooperatively regulated by dual phosphorylation of Dsn1 (a Mis12C component) and CENP-T, ensuring robust CENP-T-Mis12C interaction and proper mitotic progression. These findings deepen our understanding of kinetochores assembly in cells.

cell biology↗

bioRxiv2024

CENP-C-Mis12 complex establishes a regulatory loop through Aurora B for chromosome segregation

Establishing the correct kinetochore-microtubule attachment is crucial for faithful chromosome segregation. The kinetochore has various regulatory mechanisms for establishing correct bipolar attachment. However, how the regulations are coupled is not fully understood. Here, we demonstrate a regulatory loop between the kinetochore protein CENP-C and Aurora B kinase, which is critical for the error correction of kinetochore-microtubule attachment. This regulatory loop is mediated through the binding of CENP-C to the outer kinetochore Mis12 complex (Mis12C). Although the Mis12C binding region of CENP-C is dispensable for mouse development and proliferation in human RPE-1 cells, those cells lacking this region display increased mitotic defects. The CENP-C-Mis12C interaction facilitates the centromeric recruitment of Aurora B and the mitotic error correction in human cells. Given that Aurora B reinforces the CENP-C-Mis12C interaction, our findings reveal a positive regulatory loop between Aurora B recruitment and the CENP-C-Mis12C interaction, which ensures chromosome bi-orientation for accurate chromosome segregation.

cell biology↗