PTB deficiency causes the loss of adherens junctions in the dorsal telencephalon and leads to lethal hydrocephalus.
Polypyrimidine tract-binding protein (PTB) is a well-characterized RNA-binding protein and known to be preferentially expressed in neural stem cells (NSCs) in the central nervous system; however, its role in NSCs in the developing brain remains unclear. To explore the role of PTB in embryonic NSCs in vivo, Nestin-Cre-mediated conditional Ptb knockout mice were generated for this study. In the mutant forebrain, despite the depletion of PTB protein, neither abnormal neurogenesis nor flagrant morphological abnormalities were observed at embryonic day 14.5 (E14.5). Nevertheless, by 10 weeks, nearly all mutant mice succumbed to hydrocephalus (HC), which was caused by a lack of the ependymal cell layer in the dorsal cortex. Upon further analysis, a gradual loss of adherens junctions (AJs) was observed in the ventricular zone (VZ) of the dorsal telencephalon in the mutant brains, beginning at E14.5. In the AJs-deficient VZ, impaired interkinetic nuclear migration and precocious differentiation of NSCs were observed after E14.5. These findings demonstrated that PTB depletion in the dorsal telencephalon is causally involved in the development of HC and that PTB is important for the maintenance of AJs in the NSCs of the dorsal telencephalon.
Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, University of Tokyo, Tokyo, Japan.
Takayuki
T
Shibasaki
Akinori
A
Tokunaga
Reiko
R
Sakamoto
Hiroshi
H
Sagara
Shigeru
S
Noguchi
Toshikuni
T
Sasaoka
Nobuaki
N
Yoshida
D022005:Adherens Junctions / Q000648:ultrastructure*; D000818:Animals; D006849:Hydrocephalus / Q000209:etiology* / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000648:ultrastructure; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000502:physiology*; D013687:Telencephalon / Q000002:abnormalities / Q000196:embryology*
D038941:Polypyrimidine Tract-Binding Protein