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Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia
Published on: July 25, 2017
The mob as tumor suppressor gene is essential for early development and regulates tissue growth in Drosophila
Takeshi Shimizu1, Li-Lun Ho, Zhi-Chun Lai
1Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Abstract:
Studies in Drosophila have defined a new growth inhibitory pathway mediated by Fat (Ft), Merlin (Mer), Expanded (Ex), Hippo (Hpo), Salvador (Sav)/Shar-pei, Warts (Wts)/Large tumor suppressor (Lats), and Mob as tumor suppressor (Mats), which are all evolutionarily conserved in vertebrate animals. We previously found that the Mob family protein Mats functions as a coactivator of Wts kinase. Here we show that mats is essential for early development and is required for proper chromosomal segregation in developing embryos. Mats is expressed at low levels ubiquitously, which is consistent with the role of Mats as a general growth regulator. Like mammalian Mats, Drosophila Mats colocalizes with Wts/Lats kinase and cyclin E proteins at the centrosome. This raises the possibility that Mats may function together with Wts/Lats to regulate cyclin E activity in the centrosome for mitotic control. While Hpo/Wts signaling has been implicated in the control of cyclin E and diap1 expression, we found that it also modulates the expression of cyclin A and cyclin B. Although mats depletion leads to aberrant mitoses, this does not seem to be due to compromised mitotic spindle checkpoint function.
Insights
The Mob as tumor suppressor (Mats) protein is vital for early development and ensures correct chromosome segregation in embryos. Mats also regulates cyclin A and B expression, impacting cell division.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- The Hippo-Warts signaling pathway regulates growth and is conserved across species.
- Mob as tumor suppressor (Mats) proteins act as coactivators for Warts (Wts) kinase.
Purpose of the Study:
- To investigate the role of Mats in early development and chromosomal segregation.
- To explore the function of Mats in regulating cell cycle proteins and mitotic control.
Main Methods:
- Studied the effects of mats depletion in Drosophila embryos.
- Utilized immunofluorescence to examine protein localization at the centrosome.
- Analyzed the expression of cyclins A, B, and E.
Main Results:
- Mats is essential for embryonic development and proper chromosomal segregation.
- Mats localizes to the centrosome with Wts/Lats and cyclin E, suggesting a role in mitotic control.
- Mats depletion affects cyclin A and B expression and leads to aberrant mitoses, independent of the spindle checkpoint.
Conclusions:
- Mats plays a critical role in embryonic development and accurate chromosome segregation.
- Mats, Wts/Lats, and cyclin E may collaborate at the centrosome to regulate mitosis.
- The Hippo-Warts pathway, including Mats, influences the expression of multiple cyclins, impacting cell cycle progression.
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