Biomedical Engineering Reference
In-Depth Information
correct partition of polarity complexes (
Das, Reynolds-Kenneally, &
Mlodzik, 2002
). In zebrafish, a serine acidic amino acid-rich domain
(SE/D) in the CT of Celsr is required for membrane localization of the
Frizzled-Disheveled complex, PCP signaling, and convergent extension
(
Carreira-Barbosa et al., 2009
).
1. CELSR1
-
3 EXPRESSION PATTERNS
In mammals, the
Celsr
family is composed of three members, whereas
birds apparently lack
Celsr2
(
Formstone, 2010
) and fish have two,
Celsr1a
and
1b
(
Wada, Tanaka, Nakayama, Iwasaki, & Okamoto, 2006
). In the
mouse,
Celsr1
-
3
genes have similar genomic organizations, with 35
(
Celsr1
&
Celsr3
) or 34 exons (
Celsr2
). Apart from 3
0
alternative exons in
Celsr2
, alternative splicing has not been described.
Celsr1
-
3
expression is
regulated spatially and temporally, indicating that they are important for de-
velopment. A striking feature is the complementary pattern of
Celsr1
and
Celsr3
expressions in different developing systems (
Formstone & Little,
2001; Shima et al., 2002; Tissir, De Backer, Goffinet, & Lambert de
Rouvroit, 2002
). In the nervous system,
Celsr1
mRNA is heavily
expressed in zones of neural stem cell (NSC) proliferation, namely, all
ventricular zones during embryonic and early postnatal development, and
telencephalic ependymal zones as well as subgranular layer of the dentate
gyrus in the mature brain. In contrast,
Celsr3
mRNA is absent from NSC
and associated with most postmitotic neural cells, whereas
Celsr2
mRNA
is found in both NSC and postmitotic cells. Expression of
Celsr1
abates
during early postnatal development, in parallel to decreasing numbers of
NSC. That of
Celsr3
is downregulated postnatally but persists in the
cerebellar granular layer, the hilus of the dentate gyrus, the rostral
migratory stream, and the central region of the olfactory bulb. By
contrast,
Celsr2
expression remains stable throughout life. These
expression patterns hint to functions of
Celsr1
in NSC,
Celsr3
in neural
cell maturation, and
Celsr2
in development and maintenance of the
nervous system.
Celsr1
-
3
mRNAs are also variably expressed in
nonneural tissue, such as the skin, lungs, kidney, and digestive and
reproductive systems. In the rodent testis, the spatiotemporal pattern of
Celsr1
-
3
expression is somewhat reminiscent of that in the brain.
Celsr3
is
expressed exclusively in postmeiotic germ cells, and
Celsr1
and
Celsr2
in
Sertoli cells, with a postnatal downregulation of
Celsr1
and persistence of