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Callens, C.

Publications and source records attributed to Callens, C..

2 recordsLinked to original sources

An internal scaffold supports microtubule architectural diversity in Xenopus spermatids

During spermiogenesis, early round spermatids differentiate into specialized spermatozoa through an extensive reshaping of the nucleus driven by coordinated cytoskeletal and chromatin-based mechanisms. In mammals, this process critically relies on the transient manchette, a microtubule-based structure that remodels the spermatid nucleus and serves a track to transport material required for flagellum assembly. However, the existence, organization, and molecular composition of such a structure in other vertebrates have remained poorly investigated. Here, we establish that an organized microtubule network is present in Xenopus spermatids and shares key architectural and molecular hallmarks of the mammalian manchette. We further uncover a large structural heterogeneity of spermatid microtubules, with variable protofilament numbers, skew angles, and lattice organizations. We reveal the presence of a Spaca9-Saxo2 internal scaffold in spermatid microtubules suggesting an internal reinforcement mechanism necessary for extensive nuclear reshaping and cytoplasm remodeling.

cell biology↗

An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis

The Epithelial-Mesenchymal Transition (EMT) and primary ciliogenesis induce stem cell properties in basal Mammary Stem Cells (MaSCs) to promote mammogenesis, but the underlying mechanisms remain incompletely understood. Here, we show that EMT transcription factors promote ciliogenesis at intermediate EMT transition states by activating ciliogenesis inducers, including FGFR1. The resulting primary cilia promote BBS11-dependent ubiquitination and inactivation of a central signaling node, GLIS2. We show that GLIS2 inactivation promotes MaSC stemness, and GLIS2 is required for normal mammary gland development. Moreover, GLIS2 inactivation is required to induce the proliferative and tumorigenic capacities of the Mammary-Tumor-initiating cells (MaTICs) of claudin-low breast cancers. Claudin-low breast tumors can be segregated from other breast tumor subtypes based on a GLIS2-dependent gene expression signature. Collectively, our findings establish molecular mechanisms by which EMT programs induce ciliogenesis to control MaSC and MaTIC biology, mammary gland development, and claudin-low breast cancer formation.

cell biology↗