Differential requirements for COPI transport during vertebrate early development.
The coatomer vesicular coat complex is essential for normal Golgi and secretory activities in eukaryotic cells. Through positional cloning of genes controlling zebrafish notochord development, we found that the sneezy, happy, and dopey loci encode the alpha, beta, and beta' subunits of the coatomer complex. Export from mutant endoplasmic reticulum is blocked, Golgi structure is disrupted, and mutant embryos eventually degenerate due to widespread apoptosis. The early embryonic phenotype, however, demonstrates that despite its "housekeeping" functions, coatomer activity is specifically and cell autonomously required for normal chordamesoderm differentiation, perinotochordal basement membrane formation, and melanophore pigmentation. Hence, differential requirements for coatomer activity among embryonic tissues lead to tissue-specific developmental defects. Moreover, we note that the mRNA encoding alpha coatomer is strikingly upregulated in notochord progenitors, and we present data suggesting that alpha coatomer transcription is tuned to activity- and cell type-specific secretory loads.
Coutinho
Pedro
P
Division of Developmental Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
Parsons
Michael J
MJ
Thomas
Kevin A
KA
Hirst
Elizabeth M A
EM
Saúde
Leonor
L
Campos
Isabel
I
Williams
P Huw
PH
Stemple
Derek L
DL
D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D002454:Cell Differentiation / Q000235:genetics; D020755:Coat Protein Complex I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006056:Golgi Apparatus / Q000378:metabolism / Q000473:pathology; D008547:Melanophores / Q000502:physiology; D008648:Mesoderm; D008845:Microinjections; D018613:Microscopy, Confocal; D009672:Notochord / Q000196:embryology / Q000502:physiology / Q000648:ultrastructure; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017354:Point Mutation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D014714:Vertebrates / Q000196:embryology* / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D020755:Coat Protein Complex I; D016376:Oligonucleotides, Antisense; D021122:Protein Subunits; D012333:RNA, Messenger; D029961:Zebrafish Proteins