Biomedical Engineering Reference
In-Depth Information
causes defective mechanical flow of cerebrospinal fluid. Similar studies of
maturing ependymal cells in
Celsr2
/
mutant mice show reduced number
of cilia, abnormal organization of the cilia formed, altered tilting,
and additional defects in the apical docking of basal bodies, together
leading to little nodal flow and severe hydrocephalus (
Tissir & Goffinet,
2010
). In
Xenopus
and zebrafish, loss of Vangl2-dependent, cilia-mediated
nodal flow results in impaired left/right asymmetry (
Antic et al., 2010;
Borovina et al., 2010; May-Simera et al., 2010
). Together, these studies
have identified an important role of Vangl2 in cilial polarity and function
in different ciliated cells.
Recent genetic interaction studies and biochemical experiments have
suggested that Vangl proteins may be involved in supporting structural
integrity and function of adult tissues and organs. However, Vangl2 protein
function in adult tissues and adult tissues-related diseases has been difficult to
study, as
Vangl2
mouse mutations (
Lp
) are embryonic lethal; the recent
description of a conditional mutant allele at
Vangl2
(
Song et al., 2010
)is
likely to provide valuable information on the role of Vangl proteins in adult
tissues. Recent studies point toward a possible role for Vangl proteins in
postnatal maintenance and functions of renal tissues (
Fischer & Pontoglio,
2009
). In kidney, cilia are required for normal tubular development and
to provide environmental cues (e.g., fluid flow information) to cells bearing
them (reviewed by
Goetz & Anderson, 2010
). Single primary cilia are found
at the apex of most renal epithelial cells including the cells of the proximal
tubules, the loop of Henle, and the collecting ducts. The axoneme
and membrane of the primary cilium are formed via a highly specialized
intraflagellar transport (IFT) mechanism (
Scholey, 2008
). The IFT
system relies on kinesin and dynein motors and the associated IFT com-
plexes to organize a bidirectional retrograde and anterograde protein trans-
port. All proteins needed for ciliogenesis and/or cilia maintenance and
functions are delivered via a polarized vesicular traffic to and from the basal
bodies (
Badano et al., 2006; Nachury et al., 2007
). Mutations in
Bardet-Biedl Syndrome genes encoding proteins involved in vesicular
traffic (
Jin & Nachury, 2009; Jin et al., 2010; Nachury et al., 2007
)orin
genes encoding proteins that support integrity of the basal bodies
and transitional zone (
Gerdes et al., 2009; Williams et al., 2011
) cause a
group of recessive ciliopathies including Bardet-Biedl syndrome,
Nephronophthisis, Joubert syndrome, and Meckel-Gruber syndrome
(MKKS). These diseases have a various degree of severity (e.g., MKKS
fetuses display lethal cranial NTDs) and affect many tissues; however, all of
