It Takes Guts: The Drosophila Hindgut as a Model System for Organogenesis

Abstract

The Drosophila hindgut is fruitful territory for investigation of events common to many types of organogenesis. The development of the Drosophila hindgut provides, in microcosm, a genetic model system for studying processes such as establishment (patterning) of an epithelial primordium, its internalization by gastrulation, development of left--right asymmetric looping, patterning in both the anteroposterior and dorsoventral axes, innervation, investment of an epithelium with mesoderm, reciprocal epitheliomesenchymal interactions, cell shape change, and cell rearrangement. We review the genetic control of these processes during development of the Drosophila hindgut, and compare these to related processes in other bilaterians, particularly vertebrates. We propose that caudal/Cdx, brachyenteron/Brachyury, fork head/HNF-3, and wingless/Wnt constitute a conserved "cassette" of genes expressed in the blastopore and later in the gut, involved in posterior patterning, cell rearrangement, and gut maintenance. Elongation of the internalized Drosophila hindgut primordium is similar to elongation of the archenteron and also of the entire embryonic axis (both during and after gastrulation), as well as of various tubules (e.g., nephric ducts, Malpighian tubules), as it is driven by cell rearrangement. The genes drumstick, bowl, and lines (which encode putative transcriptional regulators) are required for this cell rearrangement, as well as for spatially localized gene expression required to establish the three morphologically distinct subregions of the hindgut. Expression of signaling molecules regulated by drumstick, bowl, and lines, in particular of the JAK/STAT activator Unpaired at the hindgut anterior, may play a role in controlling hindgut cell rearrangement. Other cell signaling molecules expressed in the hindgut epithelium are required to establish its normal size (Dpp and Hh), and to establish and maintain the hindgut visceral mesoderm (Wg and Hh). Both maternal gene activity and zygotic gene activity are required for asymmetric left--right looping of the hindgut. Some of the same genes (caudal and brachyenteron) required for embryonic hindgut development also act during pupation to construct a new hindgut from imaginal cells. Application of the plethora of genetic techniques available in Drosophila, including forward genetic screens, should identify additional genes controlling hindgut development and thus shed light on a variety of common morphogenetic processes.

Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation

“…Ihh may directly affect a wide range of target cells in both the epithelium and the mesenchyme. During morphogenesis of the fruit fly gut, the Wnt target gene Engrailed is important in the specification of the large intestine 11 . In the adult colon, Engrailed-1 is expressed in epithelial cells along the entire crypt axis, with highest expression at its base (Fig.…”

The drumstick gene acts cell-non-autonomously and triggers specification of the small intestine in the Drosophila hindgut

“…Each of these gut parts are subsequently subdivided into a number of distinct domains characterized by specific gene expression pattern (Murakami et al, 1994). These features make the Drosophila gut an attractive organ for the study of regional differentiation (Skaer, 1993;Hoch and Pankratz, 1996;Lengyel and Liu, 1998;Murakami et al, 1999;Lengyel and Iwaki, 2002). All the gut epithelia originate from anterior and posterior terminal domains of the cellular blastoderm, which form a continuous tube after invagination from both terminals.…”

“…brachyenteron (byn), a brachyury ortholog, is essential for specifying hindgut primordium (Kispert et al, 1994;Murakami et al, 1995;Singer et al, 1996). In the posterior terminal region of the cellular blastoderm, byn is activated by tll, and repressed by a hkb target gene srp, thus being restricted to a region spanning 10-15% egg length (EL) of the early cellular blastoderm, and the byn-positive region eventually forms the hindgut and anal pads Rehorn et al, 1996;Murakami et al, 1999;Lengyel and Iwaki, 2002). During embryonic development, the hindgut primordium is subdivided into several domains characterized by specific gene expression and ultrastructure (Hoch and Pankratz, 1996;Pankratz and Hoch, 1995;Murakami and Shiotsuki, 2001;Takashima and Murakami, 2001).…”

“…These results imply importance of cell-tocell interactions mediated by extracellular signal molecules in the process of subdividing hindgut into several domains. The small intestine has a couple of features similar to the rectum both in the ultrastructure and gene expression pattern: apical surface of the epithelium shows no trait of absorptive function, being covered by a thick cuticular layer; the epithelial tube is surrounded by a welldeveloped sphincter muscles (Murakami and Shiotsuki, 2001); both the small intestine and rectum express hedgehog (hh) and knirps-related (knrl) (Hoch and Pankratz, 1996;Fub et al, 2001;Takashima and Murakami, 2001;Iwaki et al, 2001;Lengyel and Iwaki, 2002;Green et al, 2002;Johansen et al, 2003). However, while the rectum is induced by Wg signaling, the small intestine is independent of Wg (Takashima and Murakami, 2001).…”

“…However, while the rectum is induced by Wg signaling, the small intestine is independent of Wg (Takashima and Murakami, 2001). Odd-family genes, drumstick (drm) and bowl, as well as Wnt-pathway related gene lines (lin), are involved in the process of fate decision of the small intestine (Iwaki et al, 2001;Lengyel and Iwaki, 2002;Green et al, 2002;Johansen et al, 2003;Hatini et al, 2005). drm is essential for the development of small intestine: drm mutant embryos fail to develop small intestine, while over-expression of drm transforms most of the hindgut primordium into small intestine.…”