Maintenance of the adult Drosophila intestine: all roads lead to homeostasis

doi:10.1016/j.gde.2016.06.009

Current Opinion in Genetics & Development

Volume 40, October 2016, Pages 81-86

https://doi.org/10.1016/j.gde.2016.06.009 Get rights and content

Maintenance of tissue homeostasis is critical in tissues with high turnover such as the intestinal epithelium. The intestinal epithelium is under constant cellular assault due to its digestive functions and its function as a barrier to chemical and bacterial insults. The resulting high rate of cellular turnover necessitates highly controlled mechanisms of regeneration to maintain the integrity of the tissue over the lifetime of the organism. Transient increase in stem cell proliferation is a commonly used and elaborate mechanism to ensure fast and efficient repair of the gut. However, tissue repair is not limited to regulating ISC proliferation, as emerging evidence demonstrates that the Drosophila intestine uses multiple strategies to ensure proper tissue homeostasis that may also extend to other tissues.

Graphical abstract

Introduction

The adult Drosophila intestine can be divided into three regions based on morphology, function, and developmental origin: the foregut, the midgut, and the hindgut [1, 2] (Figure 1a). Before 2006, the intestine was thought to be stable with little to no turnover. However, over the past ten years it has become increasingly clear that the gut is a highly dynamic tissue and that multiple mechanisms exist throughout the intestine to maintain tissue homeostasis in the face of cell turnover and damage. Here, we discuss various mechanisms used in the Drosophila adult foregut, midgut, and hindgut to maintain proper tissue homeostasis, with an emphasis on new insights gleaned in the past two to three years.

Section snippets

The foregut

The foregut, a short narrow tube located at the most anterior part of the intestine, along with the crop, cardia, and anterior-most midgut act together to store food and regulate its passage into the midgut for further processing. In 2011, using a combination of lineage tracing and molecular marker localization, Singh et al. identified a band of multipotent progenitors, referred to as gastric stem cells (GaSCs), located at the foregut/midgut boundary capable of giving rise to new cells in the

The midgut

Following the foregut is the midgut, a long tube where food undergoes digestion and absorption [2]. The midgut is surrounded by a complex network of epithelial tubules known as trachea, which deliver oxygen to the cells of the intestine [4]. In addition two layers of visceral muscle surround the midgut: an outer layer of longitudinal muscle and an inner layer of circular muscle [5]. The function of the visceral muscle is twofold; visceral muscle mediates intestinal peristalsis [6] and is an

The hindgut

The remaining portion of the intestine, the hindgut, can be further subdivided into four morphologically distinct regions: the hindgut proliferation zone (HPZ), the pylorus, the ileum, and the rectum. Located at the most anterior region of the hindgut, the HPZ is made up a narrow band of diploid cells that proliferate and differentiate in response to wingless-signaling and hedgehog-signaling. Clonal analysis by Takashima et al. [38] suggested that the HPZ contained a pool of ISCs and

Feedback regulation of intestinal cell proliferation

In the eight years since the identification of ISCs in the Drosophila midgut, a large body of literature has emerged demonstrating that midgut ISCs adjust their rates of proliferation in response to enterocyte turnover through a combination of positive and negative feedback loops initiated by enterocyte, enteroendocrine progenitor, visceral muscle, tracheal, and hemocyte derived signaling pathway ligands [7, 8, 9, 10, 11, 12, 40, 41, 42, 43, 44, 45, 46, 47, 48]. These loops act in combination

Transient amplification through delayed daughter cell amplification

Increase in ISC proliferation, following extensive cell loss, is an exquisite and effective strategy to quickly restore cell number. However, in the past few years, evidence has emerged that the Drosophila intestine uses other mechanisms to ensure tissue homeostasis is achieved following tissue injury.

Previous models describing tissue homeostasis in the midgut suggests that enteroblasts are normally produced only following cell loss, where they will then quickly differentiate into ECs, ensuring

Intestinal maintenance without stem cells

As discussed above, substantial doubt exists regarding the presence of hindgut stem cells [39^•]. In the absence of stem cells, how might tissue homeostasis be achieved? Recent investigations by two groups into the response of loss of cells from post-mitotic tissue in either the Drosophila ovary [61^••], epidermis or hindgut [62^••] revealed that nearby cells compensate for loss of cells, not by dividing, but rather by re-entering the endocycle (Figure 1 D). Re-entry into the endocycle leads to

Conclusion

Since the initial identification of intestinal stem cells in the Drosophila midgut ten years ago it has become increasingly clear that the adult fly intestine is a complex and dynamic organ. Tissue homeostasis is achieved in large part through an intricate network of injury-induced signaling pathways that feedback on ISCs to help match output to demand. Differences in stem cells exist not only between the three regions of the intestine, but between regions of the midgut and between males and

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

Supported by NIH Grant R01 DK082456-05 and ACS Grant CSM-12499 to Benjamin Ohlstein.

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Maintenance of the adult Drosophila intestine: all roads lead to homeostasis

Graphical abstract

Introduction

Section snippets

The foregut

The midgut

The hindgut

Feedback regulation of intestinal cell proliferation

Transient amplification through delayed daughter cell amplification

Intestinal maintenance without stem cells

Conclusion

References and recommended reading

Acknowledgements

Cell

Mech Dev

J Exp Biol

Insect Biochem Mol Biol

Peptides

Cell Rep

Curr Biol

Cell Rep

Cell Rep

Cell Rep

Curr Protoc Stem Cell Biol

Development

Dev Cell

Nat Cell Biol

J Cell Biol

Am J Physiol Cell Physiol

EMBO J

Stem cells in the Drosophila digestive system

Adv Exp Med Biol

The alimentary canal

The adult Drosophila gastric and stomach organs are maintained by a multipotent stem cell pool at the foregut/midgut junction in the cardia (proventriculus)

Cell Cycle

Peristalsis in the junction region of the Drosophila larval midgut is modulated by DH31 expressing enteroendocrine cells

BMC Physiol

The cellular homeostasis of the gut: what the Drosophila model points out

Histol Histopathol

Tissue communication in regenerative inflammatory signaling: lessons from the fly gut

Front Cell Infect Microbiol

The digestive tract of Drosophila melanogaster

Annu Rev Genet

The Drosophila midgut: a model for stem cell driven tissue regeneration

Wiley Interdiscip Rev Dev Biol

More Drosophila enteroendocrine peptides: Orcokinin B and the CCHamides 1 and 2

Cell Tissue Res

A subset of enteroendocrine cells is activated by amino acids in the Drosophila midgut

FEBS Lett

TrpA1 regulates defecation of food-borne pathogens under the control of the Duox pathway

PLoS Genet

The adult Drosophila posterior midgut is maintained by pluripotent stem cells

Nature

Evidence that stem cells reside in the adult Drosophila midgut epithelium

Nature

Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling

Science