Biomedical Engineering Reference
In-Depth Information
differentiate into the brain and the spinal cord of the central nervous system.
Incomplete neural tube closure causes the condition of spina bifida, the most
common disabling birth defect in the United States (
Northrup & Volcik,
2000
). Indeed, mutations in core PCP proteins (Vangl1, Vangl2,
Prickle1, Frizzled6, and Celsr1) have been recently identified in patients
with various neural tube defects (
Bosoi et al., 2011; De Marco et al.,
2012; Kibar et al., 2009; Kibar et al., 2007; Kibar et al., 2011; Kibar,
Torban, et al., 2007; Lei et al., 2010; Robinson et al., 2012
). Neural tube
closure is initiated at several places along the A-P axis forming two open
ends of the neural tube, cranial (head) end, and caudal (tail) end, also
called the anterior neuropore and the posterior neuropore. The
neuropores will ultimately close so that the neural tube becomes an
irregular tube sealed at both ends. Failure to close the anterior end or
posterior end results in anencephaly or spina bifida, respectively. If the
entire neural tube fails to close, it is referred to as craniorachischisis, a
condition that can be caused by core PCP protein mutations in mice
(
Gilbert, 2000
). While neural tube defects have been widely accepted as
one of major PCP phenotypes in mammals, caution must be taken.
Other signaling pathways, for instance, Sonic hedgehog signaling
pathway is also essential for mammalian neural tube closure (
Copp &
Greene, 2010; Copp, Greene, & Murdoch, 2003
). Perturbation of this
pathway leads to exencephaly (early stage of anencephaly) or
holoprosencephaly. Another mammalian developmental process requiring
PCP is the orientation of sensory hair cells in the cochlea of the inner ear
(
Rida & Chen, 2009; Wang & Nathans, 2007
). The sensory epithelium
has four rows of hair cells, three outer rows, and one inner row. In wild-
type mouse embryo, all hair cells orient unidirectionally. But in PCP
mutants, the orientation of hair cells becomes randomized. Both hair cell
orientation of the inner ear and neural tube closure are referred as robust
and sensitive readouts for PCP in mammalian development.
The tissue morphogenetic processes found to require PCP have
expanded in recent years (
Goodrich & Strutt, 2011; Gray et al., 2011;
Zallen, 2007
). With the generation of null mutants of both Vangl1 and
Vangl2 (
Song et al., 2010
), it is now possible to completely inactive the
Vangl-mediated PCP signaling and test the roles of PCP in these
mutants. The first directional morphogenetic process that requires PCP is
the establishment of L-R asymmetry during gastrulation (
Song et al.,
2010
). PCP is required to establish a unidirectional leftward nodal flow
when breaking the bilateral
symmetry through controlling cilium
