Altered epithelial development of the lateral ventricle choroid plexus in Mllt11 mutants

Abstract

The choroid plexuses (ChPs) are modified epithelial structures that penetrate all four cerebral ventricles and secrete cerebrospinal fluid. They consist of a central stroma that is vascularized with fenestrated blood vessels and connective tissue. The ChPs are of dual embryonic origin, with forebrain neuroepithelial cells contributing to the epithelial component and mesenchymal cells contributing to the stromal cells. The growth of the ChPs into the ventricular spaces is fueled by the migration and proliferation of neuroepithelial progenitor cells originating from the cortical hem. However, the genetic regulation of neuroepithelial progenitor (NEP) migration during ChP development is not well understood. Here we report the role of Mllt11 (Af1q/Tcf7c) in the formation of the ChP in part by regulating the migration of Otx1/2+ NEPs into the base of the fetal ChP, fueling its "treadmilling" growth into the lateral ventricle. We used Cux2iresCre/+ allele to selectively ablate Mllt11 in the developing cortical hem and its principal derivatives, the ChP and hippocampus. We discovered that Mllt11 mutants displayed thickened cuboid epithelial architecture of the ChP but maintained the epithelial organization of the outer layer of the ChP. This likely contributed to shorter lateral ventricle ChP stalks in Mllt11 cKO brains.