PATTERNING BY EGF RECEPTOR: MODELS FROM DROSOPHILA DEVELOPMENT - Complex Systems Science in Biomedicine - page 323

Figure 1 . ( A ) A mid-stage fly embryo (D = dorsal, V = ventral, A = anterior, P = posterior).
( B ) Cross-section of the embryo at the indicated plane in (Figure 1A). ( C ) The ventral ecto-
dermal cells are patterned by Egfr into two subgroups. The ventral-most cells (striped) express
all the genes listed, whereas the ventrolateral cells (dotted) express the fasciclinIII gene only
(12).
2.1. EGFR Signaling in Embryogenesis: Ventral Ectodermal Patterning
A fly embryo halfway through embryogenesis is shown in Figure 1A. Three
layers of cells are present at this stage (Figure 1B): the ectoderm, which will
form the larval epidermis; the neuroblast, which will give rise to the nervous
system; and the mesoderm, which will develop into muscle and connective tis-
sues. The midline cells, which divide the ectoderm along the dorsoventral axis,
are distinct from their neighboring ectodermal cells. These midline cells will
later delaminate from the ectoderm and give rise to specific neurons and midline
glial cells. EGFR induces two different fates in the ventral ectoderm: the ven-
tral-most and ventrolateral fates (12). The two fates are identifiable by the ex-
pression of different marker genes (Figure 1C).
The following mechanism, summarized in Figure 2, was proposed by Go-
lembo et al. (10,13,14) to explain the EGFR-mediated patterning of ventral ec-
toderm. The patterning process starts when the single-minded gene, expressed
exclusively in the midline cells, induces the expression of rhomboid (15).
Rhomboid is a protease that cleaves the Spitz transmembrane precursor into the
active secreted form (16). As a result, the midline acts as a local source of se-
creted Spitz, establishing a gradient of EGFR activation in the neighboring ecto-
dermal cells.