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Olguin, Glavic, &Mlodzik, 2011 ). Genetic screening in Drosophila identified
a set of core PCP proteins, including seven-pass transmembrane proteins
Frizzled (Fz) ( Adler, Krasnow, & Liu, 1997; Vinson & Adler, 1987 ) and
Flamingo (Fmi) ( Chae et al., 1999; Usui et al., 1999 ), a four-pass
transmembrane protein Van Gogh (Vang) ( Taylor, Abramova, Charlton,
& Adler, 1998; Wolff & Rubin, 1998 ), and cytoplasmic proteins
Disheveled (Dsh) ( Theisen et al., 1994 ), Prickle (Pk) ( Gubb et al., 1999 ),
and Diego (Dgo) ( Feiguin, Hannus, Mlodzik, & Eaton, 2001 ). The key
characteristic of these proteins is that they exhibit asymmetrical subcellular
localization once PCP is established. In the Drosophila wing cells, all these
proteins initially distribute evenly on the entire cell membrane, but during
establishment of PCP, Fz, Dsh, and Dgo preferentially accumulate to the
distal and Vang and Pk to the proximal side of cell membrane. The
atypical cadherin protein Fmi localizes both distally and proximally
( Axelrod, 2001; Chen et al., 2008; Lawrence et al., 2004; Strutt, 2001;
Tree et al., 2002; Usui et al., 1999 ). The fly harboring mutations in any
one of these core proteins displayed typical PCP phenotype in the wing,
which is randomized hair orientation. Since there are many excellent
reviews written on PCP in Drosophila ( Adler, 2002; Lawrence, Struhl, &
Casal, 2007; McNeill, 2010; Seifert & Mlodzik, 2007; Strutt, 2009; Tree
et al., 2002; Vladar et al., 2009 ), details on this subject will not be further
discussed.
In lower vertebrate model organisms, such as Xenopus and zebrafish, same
set of PCP proteins regulates a key process of gastrulation, CE ( Ciruna,
Jenny, Lee, Mlodzik, & Schier, 2006; Wallingford & Harland, 2001 ). In
this process, ML-elongated mesenchymal cells intercalate each other and
move toward the midline forcing the embryo to narrow (converge) along
the ML axis and elongate (extend) along the A-P axis concurrently
( Keller, 2002; Keller et al., 2000; Wallingford, Fraser, & Harland, 2002 ).
For example, the zebrafish trilobite mutant caused by Vangl2 (vertebrate
homologue of Drosophila Vang) mutations exhibited convergence and
extension defects with shorter and broader body axis ( Jessen et al., 2002 ).
Although the cellular signals required for CE are complicated and not yet
fully understood, impaired CE is now often viewed as an evidence of
vertebrate PCP defect.
In mammals, disrupted CE movements during mammalian neurulation
lead to failure of neural tube closure ( Tissir & Goffinet, 2010; Ueno &
Greene, 2003 ). Neurulation is a process in which the neural plate bends
up and later
fuses
to form the hollow tube that will eventually
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