The Drm–Bowl–Lin relief-of-repression hierarchy controls fore- and hindgut patterning and morphogenesis

Abstract

The elucidation of pathways linking patterning to morphogenesis is a problem of great interest. We show here that, in addition to their roles in patterning and morphogenesis of the hindgut, the Drosophila genes drumstick (drm) and bowl are required in the foregut for spatially localized gene expression and the morphogenetic processes that form the proventriculus. drm and bowl belong to a family of genes encoding C(2)H(2) zinc finger proteins; the other two members of this family are odd-skipped (odd) and sob. In both the fore- and hindgut, drm acts upstream of lines (lin), which encodes a putative transcriptional regulator, and relieves its repressive function. In spite of its phenotypic similarities with drm, bowl was found in both foregut and hindgut to act downstream, rather than upstream, of lin. These results support a hierarchy in which Drm relieves the repressive effect of Lin on Bowl, and Bowl then acts to promote spatially localized expression of genes (particularly the JAK/STAT pathway ligand encoded by upd) that control fore- and hindgut morphogenesis. Since the odd-family and lin are conserved in mosquito, mouse, and humans, we propose that the odd-family genes and lin may also interact to control patterning and morphogenesis in other insects and in vertebrates.

The Drumstick/Lines/Bowl regulatory pathway links antagonistic Hedgehog and Wingless signaling inputs to epidermal cell differentiation

“…First, we investigated the regulation of Bowl accumulation in the gut. Genetically, bowl is required both in the foregut, where it distinguishes proventriculus from anterior gut, and in hindgut, where it distinguishes small from large intestine (Iwaki et al 2001;Johansen et al 2003). Indeed, we found that Bowl protein accumulated in two narrow domains in the gut: the primordia for the proventriculus (Fig.…”

“…Similar genetic interactions between drm and lines and between lines and bowl distinguish small and large intestine in the developing hindgut, and proventriculus and foregut proper in the developing foregut (Green et al 2002;Johansen et al 2003). Bar, 10 µm.…”

“…Drm and Bowl most likely originated from a common ancestral gene by a process of gene duplication and divergence, as these genes map near one another and have a common aspect to their splicing pattern (Wang and Coulter 1996;Green et al 2002;Johansen et al 2003). Duplicated gene pairs typically perform redundant functions in a given tissue, or distinct but essential functions in different tissues as a consequence of diversification of cis-regulatory elements.…”

“…Formal genetic analysis has suggested that the three genes act in a linear genetic pathway to regulate the morphogenesis of the hindgut and foregut epithelia-lines inhibits bowl to maintain large intestine or foregut fate, respectively, except in localized areas where drm is expressed. In these areas, drm antagonizes lines, thereby allowing bowl to specify small intestine fate in the hindgut primordium and proventricular fate in the foregut primordium (Green et al 2002;Johansen et al 2003). These studies investigated neither the molecular mechanisms by which the Drm and Lines proteins regulate the activity of the Bowl protein, nor the possible involvement of this genetic pathway in other developmental processes.…”

Unbiased Screening for Transcriptional Targets of ZKSCAN3 Identifies Integrin β4 and Vascular Endothelial Growth Factor as Downstream Targets

“…for Drosophila hindgut development (14)) as a novel gene product promoting the progression of this malignancy (15). However, the mechanism by which ZKSCAN3 augmented colorectal tumorigenicity and progression was not addressed.…”