PROJECT: JTC2021 - Neurodevelopmental Disorders: NDCil

Neurodevelopmental ciliopathies: a multimodel approach from molecular mechanisms to patients variant interpretation and treatment strategies


Neurodevelopmental abnormalities resulting in life-long disability are a major feature of inherited ciliopathy disorders. Primary cilia are found on most cell surfaces, including neurons and astrocytes, and play key signalling roles during development. However, little is known about ciliary function/dysfunction in the brain, and no therapies exist for these disorders. Moreover, several patients carry “variants of unknown significance” (VUS), whose pathogenic impact remains unknown. To address these shortfalls, NDCil will focus on 4 major genes causing the archetypal neurodevelopmental ciliopathy, Joubert Syndrome (JS), and will employ complementary in vitro and in vivo models and wide-ranging techniques (CRISPR, proteomics, transcriptomics, 2D/3D cell imaging, high throughput drug screening) to characterize and compare a wealth of variants (mainly VUS) identified in JS patients. Aims of NDCil are: i) to increase knowledge of cilia in neural development and disease at multiple scales (from the subciliary TZ compartment to neurons, to the whole brain); ii) to correlate specific patients’ mutations with JS mechanisms and improve VUS interpretation; iii) to explore novel therapeutic approaches via drug repurposing strategies. Together, our interdisciplinary consortium of 5 partners provides a platform for assessing and remedying the effects of specific mutations on neurodevelopment processes, with expected benefits on diagnosis, prognosis and counselling.


Stem cells and neural differentiation/cell therapy, (epi)genetic approaches, omics approaches, Animal studies, neurodevelopmental ciliopathies; Joubert syndrome; primary cilium; genotype-phenotype correlations; drug screening

Call topic

Neurodevelopmental Disorders

Proposed runtime

n/a - n/a

Project team

Enza Maria Valente (Coordinator)
Italy (MOH)
Sylvie Schneider-Maunoury
France (ANR)
Oliver Blacque
Ireland (HRB)
Marius Ueffing
Germany (BMBF)
Andras Dinnyes
Hungary (NKFI)

Lay summary