Biomedical Engineering Reference
In-Depth Information
chondrocytes. Recent studies identified altered shapes and dimensions of
early limb buds in
Lp/Lp
embryos, lack of chondrogenic condensation
due to increased cell death in distal limbs, and digits and limb defects includ-
ing loss of phalanges and nails (
Wang, Sinha, Jiao, Serra, & Wang, 2011
).
Lp/Lp
embryos also show severe thoracic skeletal defects in the form of solid
asymmetrical sternum lacking segmentation; fused ribs and lack of vertebral
rib fusion; and abnormal size, shape, and position of vertebrae which are fre-
quently fused (
Stein & Mackensen, 1957
). In the developing eye at E16.5,
Vangl2 protein is expressed in the cornea and in migrating peridermal cells at
the time of eyelid closure, immediately prior to keratinization of the fused
eyelids (
Torban et al., 2007
);
Lp/Lp
embryos exhibit a defect in eyelid clo-
sure (
Greene et al., 1998; Torban et al., 2008
).
Vangl2 is also required for asymmetric cell division and specification of
different cell types (reviewed in
Wansleeben & Meijlink, 2011
). For exam-
ple, examination of
Lp/Lp
brain shows a decrease in the size of the neocortex
that is caused by the premature differentiation of the neuronal progenitors at
the expense of later born neurons (
Lake & Sokol, 2009
). These and addi-
tional studies
in vitro
demonstrated a role for Vangl2 in suppressing progen-
itor differentiation and promoting cell fate diversity. Vangl2 appeared to
control spindle orientation in neuronal precursors, thereby promoting
asymmetric cell division during neuronal fate specification (
Lake & Sokol,
2009
). Further, Vangl2 is also required for tangential migration of bran-
chiomotor neurons (
Bingham, Higashijima, Okamoto, & Chandrasekhar,
2002; Bingham et al., 2010; Jessen et al., 2002
), anterior-posterior
patterning of the axons of the monoaminergic neurons in brainstem
(
Fenstermaker et al., 2010
), and an establishment of the retinal axon
trajectories (
Rachel et al., 2000
). Elimination of
Vangl2
in
Lp
mice or in
other animal models causes alterations in these neuronal populations.
3. ROLE OF VANGL2 IN STRUCTURE AND FUNCTION
OF CILIATED CELLS
A role of PCP proteins, in general, and Vangl2 in particular, in the
structure and function of motile and sensory cilia has recently emerged
(
Wallingford &Mitchell, 2011
). Motile and sensory cilia project from many
cell types. While primary cilia transmit key environmental and mechanical
cues to the cells bearing them, motile cilia generate fluid flow of critical
physiological importance in the lungs, reproductive tract, and central ner-
vous system. Cilia are essential for normal vertebrate development, as they
