Fringe-dependent separation of dorsal and ventral cells in the Drosophila wing

Abstract

The separation of cells into populations that do not intermix, termed compartments, is a fundamental organizing principle during development. Dorsal-ventral compartmentalization of the Drosophila wing is regulated downstream of the apterous (ap) gene, which encodes a transcription factor that specifies dorsal wing fate. fringe (fng) is normally expressed by dorsal cells downstream of ap; here we show that fng plays a key role in dorsal-ventral compartmentalization. Loss of fng function causes dorsal cells to violate the compartment boundary, and ectopic expression of the Fng protein causes ventral cells to violate thecompartment boundary. Fng modulates signalling through the Notch receptor. Notch and its ligands are essential for formation of the dorsal-ventral compartment border, and repositioning the stripe of Notch activation that is normally established there appears to reposition the compartment border. However, activation of Notch does not itself confer either dorsal or ventral cell location, and fng can influence compartmentalization even within regions of ubiquitous Notch activation. Our results indicate that the primary mechanism by which fng establishes a compartment border is by positioning a stripe of Notch activation, but also that fng may exert additional influences on compartmentalization.

Two Distinct E3 Ubiquitin Ligases Have Complementary Functions in the Regulation of Delta and Serrate Signaling in Drosophila

“…High levels of Ser in dorsal cells activate N in trans in ventral cells and suppress N activation in cis in dorsal cells, whereas Fringe modifies N in dorsal cells such that dorsal cells located at the D-V boundary respond to Dl. Thus, composite signaling by Ser and Dl leads to symmetric N activation in margin cells located along the D-V boundary [8,9,42,43]. N then regulates the expression of the vestigial and wingless (wg) genes that cooperate to promote growth of the wing pouch.…”

Establishment and maintenance of compartmental boundaries: role of contractile actomyosin barriers

“…1a) [29][30][31][32][33]. Apterous could promote D/V cell sorting by two mechanisms: directly through targets proposed to be adhesion molecules and indirectly by inducing expression of the Notch regulator fringe in dorsal cells, a prerequisite to activate Notch in boundary cells.…”

“…Alternately, an additional signal could act redundantly with Wingless. Bidirectional signalling is necessary to implement cell sorting at the Drosophila wing disc D/V boundary (Notch/Notch) and A/P boundary (Dpp/Hh), as well as at vertebrate rhombomeres boundaries (Eph/Ephrin) [24,[26][27][28][29][30][35][36][37]. Because actomyosin accumulates asymmetrically at the interfaces of parasegmental boundary cells [50], bidirectional signalling might be involved here as well.…”

“…For D/V compartmentalization, the transcription factor Apterous-the determinant of dorsal identity-acts in conjunction with Notch signalling to position the boundary (Fig. 1a) [29][30][31][32][33]. In the vertebrate hindbrain, Notch and Eph-Ephrin bidirectional signalling are necessary for correct cell sorting at rhombomere boundaries [34][35][36][37].…”

Chip physically interacts with Notch and their stoichiometry is critical for Notch function in wing development and cell proliferation in Drosophila

“…One model proposes that in addition to its role in Notch signaling, Fringe can generate an affinity difference between dorsal and ventral cells in DV boundary in a Notch-independent manner [51,52]. Another model suggests that Notch activity is sufficient to establish an affinity difference between dorsal and ventral cells in DV boundary [22,53].…”