Localized Wnt-signaling promotes asymmetric NuMA-dependent oriented divisions and unequal apportioning of mitochondria

ABSTRACT: In multicellular organisms, the execution of developmental and homeostatic programs often rely on asymmetric cell divisions. These divisions require the alignment of the mitotic spindle axis to cortical polarity cues, and the unequal partitioning of cellular components between progeny cells. Asymmetric divisions are orchestrated by niche signals frequently presented in a directional manner, such as Wnt signals. Here we employ bioengineered Wnt-niches to demonstrate that in metaphase NuMA/dynein microtubule motors form a complex with Lrp6 and -catenin at the cortical sites of Wnt activation to orient cell division perpendicularly. We show that engagement of Lrp6 receptors by Wnt ligands locally stabilizes actomyosin contractility through the accumulation of myosin-1c. Additionally, we developed a proteomic-based approach to identify mitotic protein networks enriched at the Wnt-contact site, revealing that mitochondria polarize toward localized Wnt sources and are asymmetrically partitioned to the Wnt-proximal daughter cell during Wnt-mediated asymmetric cell division of embryonic stem cells. Our findings enhance the understanding of mitotic Wnt-signaling, and elucidate fundamental principles underlying Wnt-dependent cell polarization.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: simone tamburri  

LAB HEAD: Marina Mapelli

PROVIDER: PXD069774 | Pride | 2025-12-08

REPOSITORIES: Pride