Patterning Defects in the Primary Axonal Scaffolds
Caused by the Mutations of the Extradenticle and
Homothorax Genes in the Embryonic Drosophila Brain
Tomoko Nagao1, Keita Endo1, Hiroshi Kawauchi1, Uwe Walldorf2, Katsuo Furukubo-Tokunaga1*
1Institute of Biological Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
2Institute of Genetics, University of Hohenheim, Garbenstrasse 30, D-70599 Stuttgart, German
Originially published in: Dev. Genes Evol., 2000, 210:289-299.
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During early brain development in Drosophila, a highly stereotyped pattern
of axonal scaffolds evolves by precise pioneering and selective fasciculation of
neural fibers in the newly formed brain neuromeres (Therianos et al., 1995;
Nassif et al., 1998). Using an axonal marker, Fasciclin II (Grenningloh et al.,
1991), we show that the activities of the extradenticle (exd) and
homothorax (hth) genes (Wieschaus et al. 1984; Rauskolb et al.
1993; Rieckhof et al. 1997; Kurant et al. 1998; Pai et al. 1998) are essential to
this axonal patterning in the embryonic brain. Both genes are expressed in the
developing brain neurons including many of the tract founder cluster cells.
Consistent with their expression profiles, mutations of exd and hth
strongly perturb the primary axonal scaffolds. Furthermore, we show that
mutations of exd and hth result in profound patterning defects of the developing
brain at the molecular level including stimulation of the orthodenticle
(Finkelstein et al., 1990) gene and suppression of the empty spiracles
(Dalton et al., 1989; Walldorf et al., 1992) and cervical homeotic genes
(Mahaffey et al., 1989; Diederich et al., 1991; Hirth et al., 1998). In
addition, expression of a Drosophila Pax6 gene, eyeless
(Quiring et al., 1994), is significantly suppressed in the mutants except for the
most anterior region. The EXD and HTH proteins were originally implicated as
cofactors of the homeotic complex (HOM-C) proteins and are known to cooperatively
bind target sequences with HOM-C proteins (reviewed in Mann and Chan 1996; Mann
and Affolter 1998). Our results demonstrate that, in addition to their homeotic
regulatory functions in trunk development, exd and hth have
important functions in patterning the primary axonal scaffolds in the developing
brain, and imply molecular commonalities between the developmental mechanisms of
the brain and trunk segments, which were conventionally considered to be largely
Figure 1 - Expression of the EXD and HTH proteins in the developing brain.
Figure 2 - Coexpression of the EXD and HTH proteins with neuraxial patterning genes.
Figure 3 - Axonal tract defects in exd and hth mutant brains.
Figure 4 - Expression of neuraxial patterning genes in exd mutant brain.
Figure 5 - Expression of EY in wild type and exd mutant brains.
Figure 6 - Expression of EN and BSH in wild type and mutant brains.
Figure 7 - Summary diagrams of the neuromeric organization of the embryonic Drosophila brain.
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