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.

Braincils: Exploring the missing link between neuronal primary cilia dysfunction and neurodevelopmental disorders - hints from dental stem cell-derived brain organoids

A cell-autonomous role for primary cilia in long-range commissural axon guidance

The connection between primary cilia and the hypoxia-inducible factor-2alpha promotes the MEK/ERK signaling pathway

Growth/differentiation factor 15 influences primary cilia in neural stem cells in the ventricular-subventricular zone but not in the subgranular zone

Knockdown of Primary Ciliary Component Gene in Hypothalamic Paraventricular Nucleus Oxytocin Neurons Impairs Social Behavior

Role of the neuronal primary cilia-autophagy axis in the regulation of cognition during aging

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