Mutations in the heterotopia gene Eml1/EML1 severely disrupt the formation of primary cilia

UZQUIANO, A.; CIFUENTES-DIAZ, C.; JABALI, A.; ROMERO, D.M.; HOULLIER, A.; DINGLI, F.; MAILLARD, C.; BOLAND, A.; DELEUZE, J.F.; LOEW, D.; MANCINI, G.; BAHI-BUISSON, N.; LEDEWIG, J.; FRANCIS, F.

CELL REPORTS

CELL PRESS

Año: 2019

2211-1247

Apical radial glia (aRGs) are predominant progenitorsduring corticogenesis. Perturbing their functionleads to cortical malformations, including subcorticalheterotopia (SH), characterized by the presence ofneurons below the cortex. EML1/Eml1 mutationslead to SH in patients, as well as to heterotopic cortex(HeCo) mutant mice. In HeCo mice, some aRGsare abnormally positioned away from the ventricularzone (VZ). Thus, unraveling EML1/Eml1 function willclarify mechanisms maintaining aRGs in the VZ. Wepinpoint an unknown EML1/Eml1 function in primarycilium formation. In HeCo aRGs, cilia are shorter, lessnumerous, and often found aberrantly oriented withinvesicles. Patient fibroblasts and human corticalprogenitors show similar defects. EML1 interactswith RPGRIP1L, a ciliary protein, and RPGRIP1Lmutations were revealed in a heterotopia patient.We also identify Golgi apparatus abnormalities inEML1/Eml1 mutant cells, potentially upstream ofthe cilia phenotype. We thus reveal primary ciliamechanisms impacting aRG dynamics in physiologicaland pathological conditions.