Jump to contentJump to search

Our research

Reiff Lab in 2023 | FLTR: Mirna, Natalie, Oksana, Lisa, Tobi, Kristina, Bahram & Rita

RG Reiff

Our research:

In our laboratory, we aim to identify and describe signaling pathways controlling homeostasis and organ size of the adult Drosophila melanogaster intestine. Acting on stem cells, these signaling pathways control their proliferation, differentiation and survival in physiology, but also pathologies like colorectal cancer. An advantage of working in Drosophila´s intestine is its comparably simple tissue architecture consisting of only four major cell types: Aforementioned intestinal stem cells (ISC) that either divide symmetrically to increase the stem cell pool or divide asymmetrically to form two types of precursor cells. Enteroblasts (EB) are committed progenitors differentiating into absorptive enterocytes (EC), whereas enteroendocrine precursors (EEP) give rise to two enteroendocrine (EE) cells upon one further division cycle.

To identify and trace stem cells and their derivatives in the adult intestine, we developed a new tracing method called ‘ReDDM’ (Repressible Dual Differential Marker), that in combination with cell type specific Gal4-drivers for ISC and/or EB, ReDDM enables us to follow the ‘production’ from stem cell divisions and obtain data from the whole stem cell population. We were able to demonstrate that EB are motile entities and are able to delay terminal differentiation. By discovering that even EB survival is controlled by factors known from ISC proliferation, we added important new understanding of how intestinal homeostasis is kept in balance (Antonello et al 2015a, Antonello et al 2015b, Reiff et al 2019).

Recently, we discovered that a complex cascade of effects elicited by a neuroendocrine hormone initiates growth and reprogramming of the female intestine as an adaptation for the higher energy demand of reproduction. Mating stimulates the release of juvenile hormone (JH) from the corpus allatum (CA), a neuroendocrine gland in the adult Drosophila brain, which in turn directly acts on JH-receptors Met (methoprene-tolerant) and gce (germ cells-expressed) in EC to enhance lipid uptake and signals to ISC to stimulate proliferation. This boost in proliferation results in an increased intestinal diameter and cell number and revealed a new control mechanism of adult organ plasticity and physiological adaptations to pregnancy through a systemic hormone (Reiff et al 2015). On a whole organism level, we could show that in parallel to local signaling cues, stem cell proliferation and hence organ size can be (re-)set through neuroendocrine signaling from the brain, by the same signal that stimulates egg production. Drosophila’s brain hereby functions as a ‘integration hub’, sending and receiving signals to monitor and control an organism´s energy and reproductive status.

 

At HHU, we continue investigating hormonal control of ISC and EB behavior under physiological homeostasis. In additions, we broaden our focus into understanding pathological conditions resulting from deranged tissue homeostasis like colorectal cancer and possible implications of hormonal signaling. An ongoing investigation of the steroid hormone Ecdysone and its downstream effectors indeed proves an important role of hormone signaling in a hyperplastic model of gut tumors (Zipper et al 2020). In future experiments, we will further detail on systemic roles but also intracellular effectors of hormonal signaling pathways and aim to discover their implications in intestinal stem cell physiology and pathology.

 

Our supporters:

 

 

 

Bibliography:

Zipper L, Wagener R, Fischer U, Hoffmann A, Yasin L, Brandes D, Soura S, Anwar A, Walter C, Varghese J,  Hauer J, Auer F, Bhatia S, Dugas M, Junk S, Stanulla M, Haas O, Borkhardt A, Reiff T*, Brozou T*
“High-hyperdiploid acute lymphoblastic leukemia in children with LZTR1 germline variants”
[OA], HemaSphere, 2024, 8 (1)

Hodge RA, Ghannam M, Edmond E, de la Torre F, D’Alterio C, Kaya NH, Resnik-Docampo M, Reiff T* and D. L. Jones*
“The septate junction component Bark beetle is required for Drosophila intestinal barrier function and homeostasis”
[OA], iScience, 2023, 26 (6), 106901

Zipper L, Batchu S, Kaya NH, Antonello Z, Reiff T
"The microRNA miR-277 regulates stem cell metabolism by regulating fatty acid β-oxidation affecting physiology and pathology of the adult Drosophila midgut."
[OA], Metabolites, 2022, Vol.12 Issue4

Reiff T, Baeumers M, Tibbe C, Klein T
“Unravelling of Hidden Secrets: The Tumour Suppressor Lethal (2) Giant Discs (Lgd)/CC2D1, Notch Signalling and Cancer”
Adv Exp Med Biol 2021 Vol. 1287 Pages 31-46

Zipper L, Jassmann D, Görlich B, Reiff T. 2020. Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARγ-homologue E75B in Drosophila. bioRxiv: 2020.02.24.962829

Reiff T, Antonello ZA, Ballesta-Illán E, Mira L, Sala S, et al. 2019. Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila. The EMBO Journal 0: e101346

Antonello ZA, Reiff T, Dominguez M. 2015b. Mesenchymal to epithelial transition during tissue homeostasis and regeneration: Patching up the Drosophila midgut epithelium. Fly (Austin) 9: 132-37

Antonello ZA, Reiff T, Ballesta-Illan E, Dominguez M. 2015a. Robust intestinal homeostasis relies on cellular plasticity in enteroblasts mediated by miR-8-Escargot switch. EMBO J 34: 2025-41

Reiff T, Jacobson J, Cognigni P, Antonello Z, Ballesta E, et al. 2015. Endocrine remodelling of the adult intestine sustains reproduction in Drosophila. Elife 4: e06930

http://www.desciphered.com/portfolio/sex-makes-female-flies-fatter/

https://www.stammzellen.nrw.de/en/research/research-groups/rg-intestinal-stem-cells-in-physiology-and-pathology


Figures and images created and edited by Nida Kaya, Lisa Zipper and Tobias Reiff (2020).

 

Lab pictures

Reiff Lab in July 2018 | FLTR: Kathrin Piasecki, Tobias Reiff, Sofie Burgmer, Denise Jassmann

Christmas 2018 | Scotties

Responsible for the content: