Biomedical Engineering Reference
In-Depth Information
-
/
-
+/+
-
/
-
+/+
500
m
m
500
m
m
Figure 7.2 Hair patterning defects in Celsr1 knockout mice. In normal mice (þ/þ, left),
all body hairs point caudally and limb hairs point distally. Celsr1mutant mice (/, right)
have fur whorls and crests variably located on the head, body, and on lower dorsal
hindlimbs, where the trait is fully penetrant. Lower panels show whole mount prepara-
tions of skin at P1, stained with hematoxylin eosin to visualize disoriented hair follicles in
the mutant (
/
, right) as compared to the wild type (
þ
/
þ
, right).
homozygous
Crsh
mutation. In mutant embryos, Celsr1 protein is produced
as in the wild type, but no longer asymmetrically distributed. Moreover, the
membrane recruitment of Fzd6 and the asymmetric localization of Vangl2
along the A/P axis are compromised, with some Vangl2 immunoreactivity
forming intracellular puncta. Taken together, these results demonstrate that
Celsr1 plays a critical role for PCP establishment in the developing skin and
hair follicles (
Devenport & Fuchs, 2008
).
Importantly, PCP phenotypes in
Celsr1
mutants were also seen in mice
with mutations in other core PCP genes (
Table 7.1
). The inner ear phenotype
was reported in mice with mutated
Vangl2
(
Montcouquiol et al., 2003, 2006
),
and
Fzd3
and
Fzd6
(
Wang et al., 2006
). Neural tube closure defects were
observed in
Vangl2
, double
Dvl1
and
2
,and
Fzd3
and
6
(
Kibar et al., 2001;
Wang et al., 2006; Ybot-Gonzalez et al., 2007
). Skin hair patterning defects
were described in
Fzd6
and
Vangl2
(
Devenport & Fuchs, 2008; Devenport,
