Spatially localized Kuzbanian required for specific activation of Notch during border cell migration.

TitleSpatially localized Kuzbanian required for specific activation of Notch during border cell migration.
Publication TypeJournal Article
Year of Publication2007
AuthorsWang X, Adam JC, Montell D
JournalDev Biol
Date Published2007 Jan 15
KeywordsAmino Acid Motifs, Animals, Cell Differentiation, Cell Movement, Cell Shape, Disintegrins, Drosophila melanogaster, Drosophila Proteins, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Metalloendopeptidases, Mutation, Receptors, Notch

<p>The transmembrane receptor Notch is used repeatedly during development for a variety of essential functions. During Drosophila oogenesis, Notch activity is required first to specify particular follicle cell fates, then to promote the differentiation of all follicle cell types, to promote border cell migration, and then to form dorsal appendages, raising the question as to how Notch activity is spatially and temporally regulated. Here we show the Notch activity pattern during oogenesis. Notch activation was found in many follicle cells at stage 6 but then at stage 9 was restricted to migrating border cells, despite uniform expression of Delta. Expression of Kuzbanian (KUZ), a metalloproteinase that can activate Notch as well as cleave other substrates, is enriched in border cells at stage 9; and dominant-negative KUZ caused a strong border cell migration defect, without affecting expression of markers of border cell fate or follicle cell differentiation. Constitutively active Notch rescued the migration defect due to dominant-negative KUZ, and conditional alleles of Delta and Notch also exhibited border cell migration defects. Expression of two different reporters of Notch activity was lost upon expression of dominant-negative KUZ. Taken together these results show that Notch activation and KUZ expression are restricted to border cells at stage 9 of oogenesis and are required for migration, but not differentiation, of these cells. This represents a previously unrecognized mechanism for achieving spatial restriction of Notch signaling.</p>

Alternate JournalDev Biol
PubMed ID17010965
Grant ListR01 AG063907 / AG / NIA NIH HHS / United States
R01 GM073164 / GM / NIGMS NIH HHS / United States
U54 GM64346 / GM / NIGMS NIH HHS / United States