March 31 FOS-1 Anchor Cell Invasion

March 31 FOS-1 Anchor Cell Invasion - elegans...

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FOS-1 Promotes Basement- Membrane Removal during  Anchor-Cell Invasion in  C.  elegans Sherwood  et al ., 2005 Bisi A., Clarence H., Nicole L. March 31, 2010
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Cell invasion is a crucial part of  many cellular processes a) Development and gastrulation Epiblast cells invade at primitive streak b) Cancer metastasis Tumor cells breach  basement membrane,  invade stromal matrix c) Immune surveillance Leukocytes cross  Rowe and Weiss, 2008 (Figure 2)
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Cell invasion is part of normal  morphogenesis C. elegans  vulval  development Anchor Cell (AC):  gonadal  cell that directs  development of vulval  epithelium AC invasion stimulated by  cue from 1° vulval cells  (Sherwood and Sternberg,  Weldhaas  et al ., 2006  (Figure 1)
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AC signaling induces vulval cell  fate Mature vulva contains 22 cells,  from ectodermal cells from P  blastomere Six P cells have potential to  become vulval cells Cell fate is determined by  signals from the anchor cell Defects in AC produce mutant  phenotypes such as everted or  protruding vulva, or vulvaless  http://www.wormbook.org/chapters/www_vulvaldev/vulvaldev.h tml
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AC signaling and the role of LIN  -3 Fate of three vulval  precursor cells specified  by inductive signal from  AC 1° fate: P6.p 2° fate: P5.p, P7.p 3° fate: P cells lacking  AC signal LIN-3 induces 1° fate by  binding to LET-23  receptor epidermis AC Inductive signal (LIN-3) Lateral signal LIN-12 LET- 23 Inhibitory signal
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P cell fates are induced by lateral  inhibition Post-induction, 1° cell  inhibits neighbours  from expressing 1°  fate Inhibition induces 2°  fate Involves Notch signaling  pathway mediated by LIN- 12 receptor (Komatsu  et al .,  2008) epidermis AC Inductive signal (LIN-3) Lateral signal LIN-12 LET-23 Inhibitory signal
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Properties of  fos-1  and FOS-1 fos-1 FOS-1 Generates 2 transcripts  (A, B) Has a serine- and  threonine-rich carboxyl  terminus Important  phosphorylation sites FOS-1A FOS-1B Sherwood  et al ., 2005 (Figure 2A) http://www.uniprot.org
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Role of  fos-1  in AC invasion Primary vulval cells stimulate  AC invasion by indirectly  regulating  fos-1a  expression Involved in process of  breaching basement membrane fos-1a  regulates downstream  target genes involved in AC  invasion Sherwood  et al ., 2005. (Figure 7)
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fos-1a  regulates 3 target genes in  the anchor cell zmp-1 Z inc  M etallo P rotease Protein expressed in AC at time of basement membrane invasion (L3 larval stage), localized at basement membrane cdh-3 C a DH erin family http://www.wormbase.org
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March 31 FOS-1 Anchor Cell Invasion - elegans...

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