Roles for IFT172 and primary cilia in cell migration, cell division and neocortex development

Michal Pruski, Ling Hu, Cuiping Yang, Yubing Wang, Jin-Bao Zhang, Lei Zhang, Ying Huang, Ann M. Rajnicek, David St Clair, Colin D. McCaig, Bing Lang* (Corresponding Author), Yu-Qiang Ding* (Corresponding Author)

*Corresponding author for this work

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Abstract

The cilium of a cell translates varied extracellular cues into intracellular signals that control embryonic development and organ function. The dynamic maintenance of ciliary structure and function requires balanced bidirectional cargo transport involving Intraflagellar Transport (IFT) complexes. IFT172 is a member of the IFT complex B, and IFT172 mutation is associated with pathologies including short rib thoracic dysplasia, retinitis pigmentosa and Bardet-Biedl syndrome, but how it underpins these conditions is not clear. We used the WIM cell line, derived from embryonic fibroblasts of Wimple mice (carrying homozygous Leu1564Pro mutation in Ift172), to probe roles of Ift172 and primary cilia in cell behaviour. WIM cells had ablated cilia and deficiencies in directed migration (electrotaxis), cell proliferation and intracellular signalling. Additionally, WIM cells displayed altered cell cycle progression, with increased numbers of chromatids, highlighting dysfunctional centrosome status. Exposure to a physiological electric field promoted a higher percentage of primary cilia in wild-type cells. Interestingly, in situ hybridization revealed an extensive and dynamic expression profile of Ift172 in both developing and adult mouse cortex. In vivo manipulation of Ift172 expression in germinal regions of embryonic mouse brains perturbed neural progenitor proliferation and radial migration of postmitotic neurons, revealing a regulatory role of Ift172 in cerebral morphogenesis. Our data suggest that Ift172 regulates a range of fundamental biological processes, highlighting the pivotal roles of the primary cilium in cell physiology and brain development.
Original languageEnglish
Article number287
JournalFrontiers in Cell and Developmental Biology
Volume7
Early online date26 Nov 2019
DOIs
Publication statusPublished - Nov 2019

Bibliographical note

This work is supported by the grants from National Natural Science Foundation of China (31528011, B.L.; 81571332, 91232724, Y.D.), Key Research and Development Program from Hunan Province (2018DK2011), Shanghai Municipal Science and Technology Major Project (2018SHZDZX01) and ZJLab. We are grateful to Prof. Tamara Caspary for providing the WIM and WT cells. M.P. was funded by
a Scottish Universities Life Sciences Alliance (SULSA) studentship to C.M. and a Scholarship from Chinese Scholarship Council (CSC). L. H. is also a Scholarship awardee of CSC.

Keywords

  • corticogenesis
  • directed migration
  • primary cilium
  • IFT172
  • neocortex

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