Biomedical Engineering Reference
In-Depth Information
positioning in the node cells (
Song et al., 2010
). The leftward nodal flow
across posterior notochord (PNC) is the earliest event in the
de novo
formation of L-R asymmetry establishing L-R asymmetry, and this
unidirectional nodal flow is generated by the posteriorly localized motile
cilia in the PNC (
Hamada, Meno, Watanabe, & Saijoh, 2002; Hirokawa,
Tanaka, Okada, & Takeda, 2006; Nonaka, Shiratori, Saijoh, & Hamada,
2002; Nonaka et al., 2005; Shiratori & Hamada, 2006
). When the core
PCP proteins Vangl1 and Vangl2 were genetically removed, cilia are
randomly positioned in the PNC cells leading to turbulent nodal flow
and randomized L-R asymmetry (
Song et al., 2010
). Similar to that
observed in
Drosophila
wing, the mouse hairs also orient predominantly in
the anterior to posterior direction (proximal to distal direction in the
limb). The mouse hair is derived from precisely orientated hair follicles
determined by planar-polarized basal epidermal cells. Disruption of core
PCP proteins, for instance, Vangl2 or Frizzled6, leads to global hair
orientation defects, with waves, whorls, and tufts over the body surface
(
Devenport & Fuchs, 2008; Guo, Hawkins, & Nathans, 2004; Wang,
Chang, & Nathans, 2010; Wang, Guo, & Nathans, 2006
).
During CE, PCP regulates cell polarity in mesenchymal cells. Recently, it
is found that in the developing limb, chondrocytes are also polarized along the
proximal-distal (P-D) axis of the limb and PCP is required for limb elonga-
tion along the P-D axis (
Gao et al., 2011; Wang, Sinha, Jiao, Serra, &Wang,
2011
), possibly through a process similar to CE (
Gao et al., 2011
). Notably,
PCP has been found to play important roles in various developmental and
physiological processes in recently years, including elongation of
craniofacial processes, axon guidance, and organogenesis of heart, lung,
kidney, and eye. PCP may also play a role in tumor formation/metastasis
(
Carroll & Das, 2011; Henderson & Chaudhry, 2011; Sugiyama, Lovicu,
& McAvoy, 2011; Tissir & Goffinet, 2010; Topczewski, Dale, & Sisson,
2011; Wang, 2009; Yates & Dean, 2011
).
2.2. Global cues and PCP
Over the past 10 years, despite a growing list of diverse roles of PCP genes in
development and disease has been shown, little is known about the mech-
anism of PCP initiation and establishment. Two classes of models, a global
module and a local module, mostly based on studies in
Drosophila
, have been
proposed (
Axelrod, 2009; Axelrod & Tomlin, 2011; Blair, 2012; Strutt,
2009; Wu & Mlodzik, 2009
). The local module describes the interaction
