Genetic Cross‐Talk During Head Development in Drosophila

Abstract

The dorsal head vertex of Drosophila is specified mainly by the orthodenticle (otd) gene. The expression and the function of otd are regulated by the concerted action of many genes including hedgehog (hh) and notch (N). These genes are components of a meshwork of signaling transduction pathways that interact to form the dorsal head capsule of the fruit fly. Loss-of-function Hh mutants lack ocelli; however, loss-of-function N mutants lack a different domain of the dorsal head vertex. This report provides new evidence that the Hh and N pathways are two epistatic signaling cascades that act genetically upstream of the dorsal head capsule specification gene. INTRODUCTIONA breakthrough in understanding the Drosophila head development came with the identification of the orthodenticle (otd) homeobox gene. Previous analysis indicated that the otd transcription factor acts as an essential regulatory gene for establishing the eyes, antenna, and parts of brain and for the dorsal head development [1,2]. The Drosophila dorsal head capsule includes the ocellar, frons, and orbital cuticles. The ocelli are three simple lightsensitive organs on the ocellar cuticle. The development of the dorsal head occurs during the larval stages from the dorsal head primordium in eye disc. The ocellar cuticle is formed by a fusion of the two eye discs, with the medial ocellus receiving contributions from both discs.Previous work revealed several genes that might interact with otd in embryonic or imaginal disc development. Several of these are expressed in the dorsal head primordium and loss of their functions produces an otdlike phenotype. Hh signaling plays crucial roles in the development of Drosophila and vertebrate embryos. In the fly, there is a single hedgehog (hh) gene. In contrast, three different genes, sonic hedgehog (Shh), Indian hedgehog (Ihh), and desert hedgehog (Dhh) play distinct regulatory roles in mammals [3]. As a segment polarity gene, Hh initiates a conserved signaling cascade in a variety of developmental processes [4]. Hh protein binds to a multipass membrane protein, Patched (Ptc), and prevents it from inhibiting the function of a second transmembrane protein, Smoothened (Smo). This allows Smo to signal through the positive actions of Fused (Fu) and Cubitus interruptus (Ci) and the inhibitory effects of Costal2 (Cos2) and Drosophila Protein kinase A (dPKA). In other words, Ptc inhibits the activity of Smo, and consequently Hh binding to Ptc releases Smo from this inhibitory process [5,6,7,8] enabling Smo to interact with Fu, Ci, Cos2, and dPKA.Ci is a transcriptional effector of Hh signaling (reviewed in [9]). The expression of ci mRNA is repressed by engrailed (En) protein in both embryos and imaginal discs [10]. Ci is also posttranslationally regulated. In the absence of Hh stimulation, Ci is cleaved into a smaller N-terminal fragment (Ci75) which moves to the nucleus and represses Hh target genes. Upon secretion, Hh binds to Ptc and relieves the inhibitory effect that Ptc normally has on Smo. Once it is freed of the ...

The first deltex null mutant indicates tissue-specific deltex-dependent Notch signaling in Drosophila

“…The arrangement of the interocellar bristles was disorganized in 70% of these mutants (n=147). These phenotypes are also associated with a reduction in N signaling (Shellenbarger and Mohler 1975;Xu and Artavanis-Tsakonas 1990a;Amin 2004). The defects in the dx 152 ocelli were rescued by TXO5B in all individuals examined (Fig.…”

A Hh-driven gene network controls specification, pattern and size of the Drosophila simple eyes

“…Therefore, after its induction by hh signaling, an additional mechanism was required to stably maintain high levels of en expression in a hh-independent manner. It had been reported that in individuals mutant for a Notch temperature-sensitive (N ts ) allele, raised at the restrictive temperature during late larval life, the ocelli fuse (Amin, 2004), generating a 'cyclopic' ocellus similar to that observed in Df(2R)enE mosaics. To confirm the involvement of Notch signaling in ocellar development, we genetically manipulated several Notch pathway components.…”

Development of the ocellar visual system in Drosophila melanogaster

“…Development of the entire head vertex is dependent upon the activity of the Wingless (Wg), Hedgehog (Hh), Epidermal Growth Factor Receptor (Egfr), and Notch (N) signaling cascades as well as a suite of transcription factors. Disruptions of these pathways and their downstream transcriptional targets affect the development of various structures within the head vertex including the ocelli [112][113][114][115][116][117]. The following is a temporal and spatial summary of the GRNs that control head vertex development within the eye-antennal disk.…”