Triplet repeat diseases: the role of fly models in understanding disease mechanisms and designing possible therapies

Author(s):  
Zdenek Berger
Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 536
Author(s):  
Christian Osterburg ◽  
Susanne Osterburg ◽  
Huiqing Zhou ◽  
Caterina Missero ◽  
Volker Dötsch

The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the DNA binding domain cause Ectrodactyly, Ectodermal Dysplasia, characterized by limb deformation, cleft lip/palate, and ectodermal dysplasia while mutations in in the C-terminal domain of the α-isoform cause Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome, a life-threatening disorder characterized by skin fragility, severe, long-lasting skin erosions, and cleft lip/palate. The molecular disease mechanisms of these syndromes have recently become elucidated and have enhanced our understanding of the role of p63 in epidermal development. Here we review the molecular cause and functional consequences of these p63-mutations for skin development and discuss the consequences of p63 mutations for female fertility.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1331
Author(s):  
Alexane Ollivier ◽  
Maxime M. Mahe ◽  
Géraldine Guasch

The gastrointestinal tract is a continuous series of organs from the mouth to the esophagus, stomach, intestine and anus that allows digestion to occur. These organs are frequently associated with chronic stress and injury during life, subjecting these tissues to frequent regeneration and to the risk of developing disease-associated cancers. The possibility of generating human 3D culture systems, named organoids, that resemble histologically and functionally specific organs, has opened up potential applications in the analysis of the cellular and molecular mechanisms involved in epithelial wound healing and regenerative therapy. Here, we review how during normal development homeostasis takes place, and the role of the microenvironmental niche cells in the intestinal stem cell crypt as an example. Then, we introduce the notion of a perturbed niche during disease conditions affecting the esophageal–stomach junction and the colon, and describe the potential applications of organoid models in the analysis of human gastrointestinal disease mechanisms. Finally, we highlight the perspectives of organoid-based regenerative therapy to improve the repair of the epithelial barrier.


Author(s):  
Martina Poletti ◽  
Kaline Arnauts ◽  
Marc Ferrante ◽  
Tamas Korcsmaros

Abstract The gut microbiota appears to play a central role in health, and alterations in the gut microbiota are observed in both forms of Inflammatory Bowel Disease (IBD), namely Crohn’s disease and ulcerative colitis. Yet, the mechanisms behind host-microbiota interactions in IBD, especially at the intestinal epithelial cell level, are not yet fully understood. Dissecting the role of host-microbiota interactions in disease onset and progression is pivotal, and requires representative models mimicking the gastrointestinal ecosystem, including the intestinal epithelium, the gut microbiota and immune cells. New advancements in organoid microfluidics technology are facilitating the study of IBD-related microbial-epithelial crosstalk, and the discovery of novel microbial therapies. Here, we review different organoid-based ex vivo models that are currently available, and benchmark their suitability and limitations for specific research questions. Organoid applications such as patient-derived organoid biobanks for microbial screening and omics technologies are discussed, highlighting their potential to gain better mechanistic insights into disease mechanisms and eventually allowing personalized medicine.


2016 ◽  
Vol 37 (6) ◽  
pp. 609-635 ◽  
Author(s):  
Elena J. Tucker ◽  
Sonia R. Grover ◽  
Anne Bachelot ◽  
Philippe Touraine ◽  
Andrew H. Sinclair

Abstract Premature ovarian insufficiency (POI) is one form of female infertility, defined by loss of ovarian activity before the age of 40 and characterized by amenorrhea (primary or secondary) with raised gonadotropins and low estradiol. POI affects up to one in 100 females, including one in 1000 before the age of 30. Substantial evidence suggests a genetic basis for POI; however, the majority of cases remain unexplained, indicating that genes likely to be associated with this condition are yet to be discovered. This review discusses the current knowledge of the genetic basis of POI. We highlight genes typically known to cause syndromic POI that can be responsible for isolated POI. The role of mouse models in understanding POI pathogenesis is discussed, and a thorough list of candidate POI genes is provided. Identifying a genetic basis for POI has multiple advantages, such as enabling the identification of presymptomatic family members who can be offered counseling and cryopreservation of eggs before depletion, enabling personalized treatment based on the cause of an individual's condition, and providing better understanding of disease mechanisms that ultimately aid the development of improved treatments.


1997 ◽  
Vol 41 (5) ◽  
pp. 675-682 ◽  
Author(s):  
Laura Montermini ◽  
Andrea Richeter ◽  
Kenneth Morgan ◽  
Cristina M. Justice ◽  
Dominique Julien ◽  
...  

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