A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.
Development
; 145(1)2018 01 09.
Article
en En
| MEDLINE
| ID: mdl-29317443
ABSTRACT
Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 (Ccdc39) is responsible for early postnatal hydrocephalus in the progressive hydrocephalus (prh) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Plexo Coroideo
/
Regulación del Desarrollo de la Expresión Génica
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Proteínas del Citoesqueleto
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Epéndimo
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Hidrocefalia
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article