Dcas is required for importin-alpha3 nuclear export and mechano-sensory organ cell fate specification in Drosophila.
We have studied the in vivo function and tissue specificity of Dcas, the Drosophila ortholog of CAS, the importin beta-like export receptor for importin alpha. While dcas mRNA is specifically expressed in the embryonic central nervous system, Dcas protein is maternally supplied to all embryonic cells and its nuclear/cytoplasmic distribution varies in different tissues and times in development. Unexpectedly, hypomorphic alleles of dcas show specific transformations in mechano-sensory organ cell identity, characteristic of mutations that increase Notch signaling. Dcas is essential for efficient importin-alpha3 nuclear export in mechano-sensory cells and the surrounding epidermal cells and is indirectly required for the import of one component of the Notch pathway, but not others tested. We interpret the specificity of the dcas phenotype as indicating that one or more Notch signaling components are particularly sensitive to a disruption in nuclear protein import. We propose that mutations in house keeping genes often cause specific developmental phenotypes, such as those observed in many human genetic disorders.
Tekotte
Hildegard
H
Wellcome Trust Centre for Cell Biology, ICMB, King's Buildings, University of Edinburgh, Edinburgh, Scotland, EH9 3JR, UK.
Berdnik
Daniela
D
Török
Tibor
T
Buszczak
Michael
M
Jones
Lynn M
LM
Cooley
Lynn
L
Knoblich
Jürgen A
JA
Davis
Ilan
I
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D029563:Cellular Apoptosis Susceptibility Protein / Q000235:genetics*; D004265:DNA Helicases / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008465:Mechanoreceptors / Q000196:embryology*; D009024:Morphogenesis; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics; D012679:Sense Organs / Q000196:embryology*; D028901:alpha Karyopherins / Q000378:metabolism*
D029563:Cellular Apoptosis Susceptibility Protein; D029721:Drosophila Proteins; C486341:Kap-alpha3 protein, Drosophila; D012333:RNA, Messenger; D028901:alpha Karyopherins; D004265:DNA Helicases