Related Experiment Video
Updated: Jul 13, 2026
14:19
2D and 3D Human Induced Pluripotent Stem Cell-Based Models to Dissect Primary Cilium Involvement during Neocortical Development
Published on: March 25, 2022
K-Ras controls asymmetric cell divisions from the primary cilium
Rohan Chippalkatti1, Elisabeth Schaffner-Reckinger1, Anthoula Gaigneaux2
1Cancer Cell Biology and Drug Discovery group, Department of Health, Medicine and Life Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Cell Death & Disease
|July 11, 2026
Summary
K-Ras4B protein sustains cell ciliation during differentiation, controlling stem cell commitment. This finding reveals a novel role for K-Ras4B in differentiation and links RASopathies to ciliopathies.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- The Ras-MAPK pathway regulates critical cellular functions like proliferation and differentiation.
- The precise mechanisms by which Ras proteins control cell differentiation remain incompletely understood.
Purpose of the Study:
- To elucidate the role of K-Ras4B in skeletal muscle stem and progenitor cell differentiation.
- To investigate the relationship between K-Ras4B, primary cilia, and cell differentiation.
Main Methods:
- Mathematical modeling
- Single-cell RNA sequencing
- In vivo studies in zebrafish embryogenesis
- Analysis of protein localization and interactions within primary cilia
Main Results:
- K-Ras4B sustains primary cilia during differentiation, restricting the commitment of skeletal muscle stem and progenitor cells.
- Abnormal K-Ras4B levels or oncogenic mutations (K-Ras4B-G12C) disrupt normal differentiation processes.
- K-Ras4B localizes to primary cilia, where it interacts with components of the MAPK pathway (B-Raf, MEK, ERK).
- Targeted localization of K-Ras4B to cilia rescues normal differentiation, and in vivo modulation affects ciliation-dependent development.
Conclusions:
- K-Ras4B plays a fundamental, previously unrecognized role in regulating cell differentiation through the control of primary cilia.
- This study provides a mechanistic link between RASopathies and ciliopathies, explaining shared phenotypic characteristics.
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