Details

Autor(en) / Beteiligte

• Yan, Lu
• Yin, Hailing
• Mi, Yiwei
• Wu, Yu
• Zheng, Yufang

Titel

Deficiency of Wdr60 and Wdr34 cause distinct neural tube malformation phenotypes in early embryos

Ist Teil von

• Frontiers in cell and developmental biology, 2023-05, Vol.11, p.1084245-1084245

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2023

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Cilia are specialized organelles that extend from plasma membrane, functioning as antennas for signal transduction and are involved in embryonic morphogenesis. Dysfunction of cilia lead to many developmental defects, including neural tube defects (NTDs). Heterodimer - (WD repeat domain 60 and 34) are intermediate chains of motor protein dynein-2, which play important roles in ciliary retrograde transport. It has been reported that disruption of in mouse model results in NTDs and defects of Sonic Hedgehog (SHH) signaling. However, no deficiency mouse model has been reported yet. In this study, piggyBac (PB) transposon is used to interfere and expression respectively to establish and mouse models. We found that the expression of or is significantly decreased in the homozygote mice. homozygote mice die around E13.5 to E14.5, while homozygote mice die around E10.5 to E11.5. is highly expressed in the head region at E10.5 and embryos have head malformation. RNAseq and qRT-PCR experiments revealed that Sonic Hedgehog signaling is also downregulated in head tissue, demonstrating that WDR60 is also required for promoting SHH signaling. Further experiments on mouse embryos also revealed that the expression levels of planar cell polarity (PCP) components such as CELSR1 and downstream signal molecule c-Jun were downregulated in homozygotes compared to wildtype littermates. Coincidently, we observed much higher ratio of open cranial and caudal neural tube in mice. CO-IP experiment showed that and both interact with IFT88, but only interacts with IFT140. Taken together, and play overlapped and distinct functions in modulating neural tube development.