Biomedical Engineering Reference
In-Depth Information
mediolateral intercalation. CE movements are responsible for the narrowing
and lengthening of the neural plate during NT closure. Homozygosity for
mutations in
Vangl1
(
Antic et al., 2010
),
Vangl2
(
Kibar, Underhill, et al.,
2001
),
Dvl1/Dvl2
(
Wang, Guo, et al., 2006
),
Dvl2/Dvl3
(
Etheridge
et al., 2008
),
Celsr1
(
Curtin et al., 2003
),
Fz3/Fz6
(
Wang, Guo, et al.,
2006
),
Scribble
(
Murdoch et al., 2003
),
Ptk7
(
Lu et al., 2004
), and S
ec24b
(
Merte et al., 2010
) causes NTDs of different severity, including the
characteristic very severe craniorachischisis. Likewise, severe NTDs (and
the PCP defects) are often detected in mutant mice double heterozygous
for mutations in
Vangl2
(
Vangl2
Lp/
รพ
) and other PCP genes from the
above-mentioned list, highlighting the key role of
Vangl2
in this process.
CE movements are also essential for cardiogenesis; mutations in
Vangl2
and
Fz1/Fz2
cause cardiac defects in the form of aberrant right
subclavian artery and double outlet right ventricle (
Torban et al., 2008;
Yu et al., 2010
).
The careful morphological and cytological analyses of anomalies
detected in
Lp
mice have shown that, in addition to NT closure and
cardiogenesis, Vangl2-dependent PCP and CE activities, are required for
patterning of many additional tissues and organs (
Table 10.1
).
Vangl2
(and
Celsr1
) is expressed in restricted spatial domains of epithelial cells in de-
veloping lung.
Lp/Lp
embryos display defects in lung branching morpho-
genesis manifested as lung hypoplasia, reduction in number and width of
airways, thickening of the interstitial mesenchyme, defective saccular forma-
tion, and impaired branching in response to FGF10 (
Yates,
Schnatwinkel, et al., 2010
). Vangl2 protein is expressed in developing skin
(embryonic epidermis), and homozygous
Lp
embryos have hair follicles that
are misangled, with altered anterior-posterior polarization of interfollicular
epithelium (
Devenport & Fuchs, 2008
). Vangl2 is expressed at the lateral
edges of the apical pole of uterine epithelial cells, and
Lp
homozygotes display
loss of columnar appearance of uterine epithelium. As a result, the
Lp/Lp
and
Lp
heterozygotes both show gross anatomical defects of reproduction
system and the
Lp
heterozygotes are often sterile (
Vandenberg & Sassoon,
2009
). Vangl2 is expressed in the developing gut, including epithelial cells
of the developing stomach and duodenum (
Torban et al., 2007
), and
Lp/Lp
E13.5 embryos display a smaller fore-stomach with a loss of apicobasal
polarity and oriented cell division (
Matsuyama et al., 2009
). Early studies
detected
Vangl
mRNA expression in the developing limbs in the
E10.5-13.5 embryos (
Torban et al., 2008
). In addition,
Gao et al. (2011)
reported asymmetric Vangl2 protein localization in developing limbs
