Cell News 4/2014
13
Research news
been shown that calcineurin is involved in different develop-
mental processes like egg-laying, fertility, and growth (reviewed
in (Lee et al., 2013)). The role of calcineurin in muscle develop-
ment has been intensivly investigated (reviewed in (Mallinson et
al., 2009)). Also in
Drosophila melanogaster
it could be shown
that calcineurin plays a role in flight muscle development (Ga-
jewski et al., 2006). Tadpoles of the African clawed frog
Xenopus
laevis
are able to regenerate their tales after amputation. This
ability is lost in the so-called “refractory period”, a particular
developmental stage between stages 45-47 (Beck et al., 2003).
However, suppressing calcineurin with CsA or FK506 restored
the regenerative ability during the refractory period (Fukazawa
et al., 2009). Similar, calcineurin is involved in the regenerati-
on of fins in zebrafish after amputation and in the outgrowth
of developing juvenile fins (Kujawski et al., 2014). Inhibition of
calcineurin with CsA overrides the intrinsic dimensional growth
control leading to fins that are disproportionate to the body
size (longer fins). Calcineurin inhibition promotes the retinoic-
acid-mediated signalling, which is known to regulate positional
growth in developing and regenerating appendages by proxima-
lizing the outgrowth (Maden, 1982). Therefore, calcineurin can
act like a molecular switch between isometric and allometric
growth (Kujawski et al., 2014).
These examples, together with results obtained in chicks (Li-
beratore and Yutzey, 2004), demonstrate that calcineurin is
involved in developmental processes in much more higher eu-
karyotes than mammals. Further research is needed to elucidate
parallels and differences in this signalling pathway in different
species.
The role of calcineurin during development of lower
eukaryotes
Also in lower eukaryotes the phosphatase is involved in dif-
ferent developmental processes (Table 1). It has been shown
that
S. pombe
cells lacking calcineurin show branching of the
cells (Yoshida et al., 1994; Cadou et al., 2013). This phenome-
non could be explained by defects in septum formation and
separation of daughter cells. Additionally, many filamentous
fungi show hyphal defects with either a lack of branching or
hyperbranching of the hyphae if calcineurin function is impaired
(Prokisch et al., 1997; Kothe and Free, 1998; Cruz et al., 2001;
Sanglard et al., 2003; Viaud et al., 2003; Steinbach et al., 2006;
da Silva Ferreira et al., 2007; Egan et al., 2009; Cervantes-Chávez
et al., 2011; Chen et al., 2011; Kume et al., 2011; Harren et al.,
2012; Zhang et al., 2012; Juvvadi et al., 2013; Tsai and Chung,
2014). To some extend these defects can be explained by mis-
Table 1:
Overview of developmental processes in higher and lower eukaryotes with calcineurin-involvement. Only publications with direct evidence of calcineurin
involvement have been considered.
Organ/process
Reference(s)
Higher eukaryotes
Brain (neural induction, dendrite outgrowth and branching, synapse
density, neurodegeneration)
(Graef et al., 2003; Wu et al., 2010a; Spires-Jones et al., 2011;
Elmer et al., 2013; Cho et al., 2014)
Vasculature
(Graef et al., 2001)
Heart (coronary arteries, valves)
(Liberatore and Yutzey, 2004; Yang et al., 2014)
Kidney (nephrogenic zone, glomeruli)
(Gooch et al., 2004)
Thymocyte
(Neilson et al., 2004; Gallo et al., 2007)
Bone (formation and growth)
(Sun et al., 2005)
Muscle
(Gajewski et al., 2006; Mallinson et al., 2009)
Fin outgrowth (zebrafish)
(Kujawski et al., 2014)
Tadpole tail generation
(Xenopus)
(Fukazawa et al., 2009)
Lower eukaryotes
Cell morphogenesis / tip dominance / polarised growth (fungi)
(Prokisch et al., 1997; Kothe and Free, 1998; Cruz et al., 2001; Sang-
lard et al., 2003; Viaud et al., 2003; Harel et al., 2006; Steinbach et
al., 2006; da Silva Ferreira et al., 2007; Egan et al., 2009; Cervantes-
Chávez et al., 2011; Chen et al., 2011; Kume et al., 2011; Harren et al.,
2012; Zhang et al., 2012; Juvvadi et al., 2013; Tsai and Chung, 2014)
Conidiation / sclerotial development (fungi)
(Harel et al., 2006; Steinbach et al., 2006; da Silva Ferreira et al.,
2007; Harren et al., 2012; Tsai and Chung, 2014)
Fruiting body development / cell differentiation
(Dictyostelium)
(Horn and Gross, 1996; Weissenmayer et al., 2005; Boeckeler et al.,
2006; Thewes et al., 2014)
Daughter cell separation / branching
(S. pombe)
(Yoshida et al., 1994; Cadou et al., 2013)
