Primary Cilia
primary cilia
The cell biology of Parkinson’s disease: a role for primary cilia and synaptic vesicle pleomorphism in dopaminergic neurons
Modeling human brain development and disease: the role of primary cilia
Neurodevelopmental disorders (NDDs) impose a global burden, affecting an increasing number of individuals. While some causative genes have been identified, understanding the human-specific mechanisms involved in these disorders remains limited. Traditional gene-driven approaches for modeling brain diseases have failed to capture the diverse and convergent mechanisms at play. Centrosomes and cilia act as intermediaries between environmental and intrinsic signals, regulating cellular behavior. Mutations or dosage variations disrupting their function have been linked to brain formation deficits, highlighting their importance, yet their precise contributions remain largely unknown. Hence, we aim to investigate whether the centrosome/cilia axis is crucial for brain development and serves as a hub for human-specific mechanisms disrupted in NDDs. Towards this direction, we first demonstrated species-specific and cell-type-specific differences in the cilia-genes expression during mouse and human corticogenesis. Then, to dissect their role, we provoked their ectopic overexpression or silencing in the developing mouse cortex or in human brain organoids. Our findings suggest that cilia genes manipulation alters both the numbers and the position of NPCs and neurons in the developing cortex. Interestingly, primary cilium morphology is disrupted, as we find changes in their length, orientation and number that lead to disruption of the apical belt and altered delamination profiles during development. Our results give insight into the role of primary cilia in human cortical development and address fundamental questions regarding the diversity and convergence of gene function in development and disease manifestation. It has the potential to uncover novel pharmacological targets, facilitate personalized medicine, and improve the lives of individuals affected by NDDs through targeted cilia-based therapies.
Hypoxia induces MEK/ERK signaling via primary cilia and the hypoxia-inducible factor-2alpha - a helping factor for neuronal cells to survive ischemia?
FENS Forum 2024
The hypoxia-inducible factor 1alpha and primary cilia – a functional analysis of the interplay in neuronal cells
FENS Forum 2024
A novel microtubule doublet regulator in neuronal primary cilia
FENS Forum 2024
The sweet taste receptor signaling at primary cilia involves an adenylate cyclase inhibitory mechanism
FENS Forum 2024