Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis

Hirotaka Tao; Ken-ichi Inoue; Hiroshi Kiyonari; Alexander G Bassuk; Jeffrey D Axelrod; Hiroshi Sasaki; Shinichi Aizawa; Naoto Ueno

doi:10.1016/j.ydbio.2012.01.025

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Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis

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Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis

Hirotaka Tao, Ken-ichi Inoue, Hiroshi Kiyonari, Alexander G Bassuk, Jeffrey D Axelrod, Hiroshi Sasaki, Shinichi Aizawa and Naoto Ueno

Developmental biology, Vol.364(2), pp.138-148

04/15/2012

DOI: 10.1016/j.ydbio.2012.01.025

PMCID: PMC3299875

PMID: 22333836

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Abstract

The establishment of trophectoderm (TE) manifests as the formation of epithelium, and is dependent on many structural and regulatory components that are commonly found and function in many epithelial tissues. However, the mechanism of TE formation is currently not well understood. Prickle1 (Pk1), a core component of the planar cell polarity (PCP) pathway, is essential for epiblast polarization before gastrulation, yet the roles of Pk family members in early mouse embryogenesis are obscure. Here we found that Pk2−/− embryos died at E3.0–3.5 without forming the blastocyst cavity and not maintained epithelial integrity of TE. These phenotypes were due to loss of the apical–basal (AB) polarity that underlies the asymmetric redistribution of microtubule networks and proper accumulation of AB polarity components on each membrane during compaction. In addition, we found GTP-bound active form of nuclear RhoA was decreased in Pk2−/− embryos during compaction. We further show that the first cell fate decision was disrupted in Pk2−/− embryos. Interestingly, Pk2 localized to the nucleus from the 2-cell to around the 16-cell stage despite its cytoplasmic function previously reported. Inhibiting farnesylation blocked Pk2's nuclear localization and disrupted AB cell polarity, suggesting that Pk2 farnesylation is essential for its nuclear localization and function. The cell polarity phenotype was efficiently rescued by nuclear but not cytoplasmic Pk2, demonstrating the nuclear localization of Pk2 is critical for its function. ► Pk2 protein was mainly localized in the nucleus at 2-, 4-, 8-cell stages. ► Pk2−/− embryos failed to form a blastocyst cavity. ► Pk2 mediates microtubule redistribution within the cell cortex during compaction. ► The loss of Pk2 disrupts expression and localization of AB polarity components. ► The nuclear retention of Pk2 is required for the establishment of cell polarity.

Details

Title: Subtitle: Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis
Creators: Hirotaka Tao - Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology (CDB), 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-047, Japan
Ken-ichi Inoue - Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology (CDB), 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-047, Japan
Hiroshi Kiyonari - Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology (CDB), 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-047, Japan
Alexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Jeffrey D Axelrod - Department of Pathology, Stanford University school of Medicine, Stanford, CA 94305, USA
Hiroshi Sasaki - Laboratory for Embryonic induction, RIKEN Center for Developmental Biology (CDB), 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-047, Japan
Shinichi Aizawa - Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology (CDB), 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-047, Japan
Naoto Ueno - Division of Morphogenesis, National institute for Basic Biology, 38 Nishigonaka, Myoudaiji, Okazaki 444-8585, Japan
Resource Type: Journal article
Publication Details: Developmental biology, Vol.364(2), pp.138-148
DOI: 10.1016/j.ydbio.2012.01.025
PMID: 22333836
PMCID: PMC3299875
NLM abbreviation: Dev Biol
ISSN: 0012-1606
eISSN: 1095-564X
Publisher: Elsevier Inc
Grant note: name: Scientific Research, MEXT, Japan, award: 21116003, 18GS0320, 22116511, 22127007; name: NIH, award: NS064159-01A1
Language: English
Date published: 04/15/2012
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984020645902771

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