Biomedical Engineering Reference
In-Depth Information
(
Inversin
)(
McNeill, 2010; Simons & Mlodzik, 2008
), and 4
Fat
(Saburi,
2012;
Saburi et al., 2008
).
Inturned
and
fuzzy
relatives have also been
described and studied in vertebrates (
Gray et al., 2009; Heydeck, Zeng,
& Liu, 2009; Park, Haigo, & Wallingford, 2006
). Finally, a number of
PCP genes, whose mutations cause defects in planar polarity only in
vertebrates, have been identified including
Ptk7
(
Lu et al., 2004; Yen
et al., 2009
),
Scribble
(
Murdoch et al., 2003
),
Ror2
(
Gao et al., 2011
), and
Sec24b
(
Merte et al., 2010; Wansleeben et al., 2010
). The presence of
multiple paralogous PCP genes that are expressed at a variable degree of
tissue and cell specificity and often display functional redundancy has
complicated the functional characterization of individual PCP genes. In
addition, embryonic lethality caused by inactivation of some PCP genes
(
Vangl2
,
Celsr1
) has until recently precluded a study of their role in the
structure,
function,
and maintenance of
adult
tissues
and possible
association with pathologies in the adults.
At the cellular level, Vangl and other mammalian PCP proteins devel-
opmentally regulate the structure, positioning, and polarity of cellular ap-
pendages in different cell types. They are also involved in the asymmetric
morphology, polarization, oriented cell division, migration, and redistribu-
tion of many cell populations. Consequently, mutations in PCP genes have
been shown to affect biogenesis, structure, and function of a surprisingly
large number of tissues and organs (
Table 10.1
;
McNeill, 2010; Simons &
Mlodzik, 2008; Tissir & Goffinet, 2010; Wansleeben & Meijlink, 2011
).
For example, the uniform orientation of stereociliary bundles on outer
and inner hair cells of the cochlear duct (organ of Corti) is a classical
manifestation of PCP in mammals. Mutations not only in
Vangl1
(
Torban
et al., 2008
) and
Vangl2
(
Montcouquiol et al., 2003
) but also in other
PCP genes such as
Dvl1/Dvl2
(
Wang et al., 2005
),
Dvl3
(
Etheridge et al.,
2008
),
Fz3
/
Fz6
(
Wang, Guo, & Nathans, 2006
),
Fat4
(
Saburi et al.,
2008
), and
Celsr1
(
Curtin et al., 2003
) disrupt PCP of the stereociliary
bundles to a varying degree.
In vertebrates, PCP proteins also participate in morphogenic activity
designated convergent extension (CE) movements. CE plays a critical role
in several aspects of embryogenesis and this process has been particularly well
studied in
Xenopus
. CE is the process in which a tissue or epithelium narrows
in one axis and lengthens in a perpendicular axis, allowing tissue remodeling
(
Keller, 1975, 1976; Wallingford, Fraser, & Harland, 2002
). CE plays a
critical role during gastrulation, neurulation, and organogenesis. During
CE, cells form mediolateral protrusions that generate traction used for
