Mouse prickle1, the homolog of a PCP gene, is essential for epiblast apical-basal polarity.
Planar cell polarity (PCP) genes are essential for establishing planar cell polarity in both invertebrate and vertebrate tissues and are known to regulate cellular morphogenesis and cell movements during development. We focused on Prickle, one of the core components of the PCP pathway, and deleted one of two mouse prickle homologous genes, mpk1. We found that the deletion of mpk1 gene resulted in early embryonic lethality, between embryonic day (E)5.5 and E6.5, associated with failure of distal visceral endoderm migration and primitive streak formation. The mpk1(-/-) epiblast tissue was disorganized, and analyses at the cellular level revealed abnormal cell shapes, mislocalized extracellular matrix (ECM) proteins, and disrupted orientation of mitotic spindles, from which loss of apico-basal (AB) polarity of epiblast cells are suspected. Furthermore, we show mpk1 genetically interacts with another core PCP gene Vangl2/stbm in the epiblast formation, suggesting that PCP components are commonly required for the establishment and/or the maintenance of epiblast AB polarity. This was further supported by our finding that overexpression of DeltaPET/LIM (DeltaP/L), a dominant-negative Pk construct, in Xenopus embryo disrupted uniform localization of an apical marker PKCzeta, and expanded the apical domain of ectoderm cells. Our results demonstrate a role for mpk1 in AB polarity formation rather than expected role as a PCP gene.
Tao
Hirotaka
H
Division for Morphogenesis, National Institute for Basic Biology, Myodaiji, Okazaki, Aichi 444-8585, Japan.
Suzuki
Makoto
M
Kiyonari
Hiroshi
H
Abe
Takaya
T
Sasaoka
Toshikuni
T
Ueno
Naoto
N
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D000099221:Protein Kinase C zeta
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D060588:LIM Domain Proteins; D009419:Nerve Tissue Proteins; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta; C431577:Ltap protein, mouse; C524253:Prickle1 protein, mouse
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