Growth, Differentiation and Sexuality

110 J. Wendland and A. Walther
budding in baker’s yeast (Harris 1999; Wendland
and Philippsen 2001). The first round of septation
occurs at the neck separating the germ cell from
the first hypha in both organisms (Wolkow et al.
1996; Wendland and Philippsen 2000). Mutants
that interfere with the bipolar branching pattern
were also obtained. SwoA of A. nidulans encodes
a protein O-mannosyltransferase and is allelic to
pmtA (Shaw and Momany 2002). This is remarkable,
since O-glycosylation of the S. cerevisiae
landmark protein Axl2p/Bud10p is required for
the establishment of correct axial budding in
haploid (a, orα) yeast cells (Sanders et al. 1999).
Deletion of the S. cerevisiae PMT4 gene resulted
in unstable and mislocalized Axl2p/Bud10p, and
shifted the budding pattern from axial to unipolar.
A mutant branching phenotype of germ cells
similar to swoA was observed in the A. gossypii
bem2 mutant (Wendland and Philippsen 2000).
Bem2p encodes a Rho-GTPase activating protein,
and in yeast is involved in bud emergence (Bender
and Pringle 1991). Reminiscent of the germ
cell/hypha position of the first septum, swollen
A. gossypii hyphal tips of rho3 mutants generate
a septum between swellings and newly generated
hyphae (Wendland and Philippsen 2001). Adult A.
gossypii hyphae that underwent a process termed
‘hyphal maturation’ show a distinct dichotomous
tip branching pattern. Characteristically, branches
in A. gossypii become septate at their bases, so that
after tip branching two septa are formed simultaneously
(Ayad-Durieux et al. 2000; Wendland and
Philippsen 2002).
Positioning of the first septum in the dimorphic
human fungal pathogen Candida albicans appears
to be different from that documented in A.
nidulans and A. gossypii (Fig. 6.2B). C. albicans is
a dimorphic fungus that switches between yeast
and hyphal growth upon induction through environmental
stimuli (Berman and Sudbery 2002). C.
albicans yeast cells that are induced to form hyphae
do not position their first septum at the bud neck,
but rather move this septal site 10–15 μm into the
hyphal tube (Sudbery 2001). An integrin-like protein
encoded by the C. albicans INT1 gene may play
a specific role in this site selection and colocalizes
to this newly formed septal site, although the
biological significance of this process is unknown
(Gale et al. 2001).
Similarly to the early phases of hyphal development
when switching isotropic growth of germ cells
to polarized hyphal growth, other developmental
stages, particularly during conidiation (e.g., in A.
nidulans), show a specific pattern of septa positioning
(Fig. 6.2C). During conidiogenesis, hyphae
differentiate into a stalk and a vesicle from which
single cell generations called metulae, phialides,
and chains of conidia emerge (Timberlake 1990).
These single cells are uninucleate, and resemble
elongated yeast cells with unipolar budding pattern.
Understanding the molecular mechanism of
how septal sites are positioned within the growing
hyphae of filamentous fungi is of central importance
in understanding fungal biology. An interesting
finding showed that hyphal tip regions,
as well as septal sites form sterol-enriched domains,
termed lipid-rafts, which may play a key
upstream signaling role for the protein machinery
in charge of septation (Martin and Konopka 2004).
The role of the hyphal tip in positioning septal cues
has been evaluated in recent reports (Kaminskyj
2000; Knechtle et al. 2003). A decrease of polarized
growth rates was observed in juvenile mycelia
of A. gossypii that at the same time formed lateral
branches or septa at subapical positions. Positions
at which the apical extension rate was slowed down
were found to develop septa once the hyphal tip
had resumed fast growth. This indicates that the
hyphal tip is involved in placing cortical cues that
determine the position of future septa (Knechtle
et al. 2003). The molecular nature of such a mechanism
is currently unknown. Pathways that may
be involved are the Cdc42p Rho-GTPase module
that may link a tip-generated signal via the PAK
kinase Cla4p to septin family members (see below;
Ayad-Durieux et al. 2000; Schmidt et al. 2003).
In addition, landmark proteins such as Bud3p, for
example, could play an important role in this process
by linking a tip-generated signal with septum
positioning, and eventually septum construction
(Wendland 2003). Mining the N. crassa genome revealed
the presence of a number of potential BUD
gene homologs in a fungus that is more distantly
related to S. cerevisiae than to A. gossypii. This suggests
that the general mechanism of septum positioning
is conserved in filamentous ascomycetes
(Walther and Wendland 2003).
III. Protein Complexes at Septal Sites
Fungal septa are characterized by the presence of
a chitin-rich septum that is absent in animal cells
(see Sietsma and Wessels, Chap. 4, and Latgé and