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First published online 18 March 2009
doi: 10.1242/dev.028472

Development 136, 1433-1442 (2009)
Published by The Company of Biologists 2009
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C. elegans mig-6 encodes papilin isoforms that affect distinct aspects of DTC migration, and interacts genetically with mig-17 and collagen IV

Takehiro Kawano1, Hong Zheng1, David C. Merz1, Yuji Kohara2, Katsuyuki K. Tamai3, Kiyoji Nishiwaki3 and Joseph G. Culotti1,4,*

1 Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, M5G 1X5, Canada.
2 Genome Biology, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
3 RIKEN Center for Developmental Biology, Kobe, 650-0047, Japan.
4 Department of Molecular Genetics, University of Toronto, Toronto, M5S 1AB, Canada.

* Author for correspondence (e-mail: culotti{at}mshri.on.ca)

Accepted 20 February 2009

The gonad arms of C. elegans hermaphrodites acquire invariant shapes by guided migrations of distal tip cells (DTCs), which occur in three phases that differ in the direction and basement membrane substrata used for movement. We found that mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of DTC migration. Both MIG-6 isoforms have a predicted N-terminal papilin cassette, lagrin repeats and C-terminal Kunitz-type serine proteinase inhibitory domains. We show that mutations affecting MIG-6L specifically and cell-autonomously decrease the rate of post-embryonic DTC migration, mimicking a post-embryonic collagen IV deficit. We also show that MIG-6S has two separable functions - one in embryogenesis and one in the second phase of DTC migration. Genetic data suggest that MIG-6S functions in the same pathway as the MIG-17/ADAMTS metalloproteinase for guiding phase 2 DTC migrations, and MIG-17 is abnormally localized in mig-6 class-s mutants. Genetic data also suggest that MIG-6S and non-fibrillar network collagen IV play antagonistic roles to ensure normal phase 2 DTC guidance.

Key words: C. elegans, Cell migration, MIG-17/ADAMTS, MIG-6/papilin, Collagen IV


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[Abstract] [Full Text] [PDF]


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