Regulation of neurocoel morphogenesis by Pard6 gamma b.
The Par3/Par6/aPKC protein complex plays a key role in the establishment and maintenance of apicobasal polarity, a cellular characteristic essential for tissue and organ morphogenesis, differentiation and homeostasis. During a forward genetic screen for liver and pancreas mutants, we identified a pard6gammab mutant, representing the first known pard6 mutant in a vertebrate organism. pard6gammab mutants exhibit defects in epithelial tissue development as well as multiple lumens in the neural tube. Analyses of the cells lining the neural tube cavity, or neurocoel, in wildtype and pard6gammab mutant embryos show that lack of Pard6gammab function leads to defects in mitotic spindle orientation during neurulation. We also found that the PB1 (aPKC-binding) and CRIB (Cdc-42-binding) domains and the KPLG amino acid sequence within the PDZ domain (Pals1-and Crumbs binding) are not required for Pard6gammab localization but are essential for its function in neurocoel morphogenesis. Apical membranes are reduced, but not completely absent, in mutants lacking the zygotic, or both the maternal and zygotic, function of pard6gammab, leading us to examine the localization and function of the three additional zebrafish Pard6 proteins. We found that Pard6alpha, but not Pard6beta or Pard6gammaa, could partially rescue the pard6gammab(s441) mutant phenotypes. Altogether, these data indicate a previously unappreciated functional diversity and complexity within the vertebrate pard6 gene family.
Munson
Chantilly
C
Department of Biochemistry and Biophysics, Genetics and Human Genetics, University of California, San Francisco, CA 94158, USA.
Huisken
Jan
J
Bit-Avragim
Nana
N
Kuo
Taiyi
T
Dong
P D
PD
Ober
Elke A
EA
Verkade
Heather
H
Abdelilah-Seyfried
Salim
S
Stainier
Didier Y R
DY
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D016764:Cell Polarity; D004848:Epithelium / Q000196:embryology; D009024:Morphogenesis; D009154:Mutation; D054259:Neural Tube / Q000196:embryology* / Q000502:physiology; D054261:Neurulation; D008941:Spindle Apparatus / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C534334:Pard6gb protein, zebrafish; D029961:Zebrafish Proteins