scholarly journals Accelerated cell cycles enable organ regeneration under developmental time constraints in the Drosophila hindgut

2020 ◽  
Author(s):  
Erez Cohen ◽  
Donald T. Fox

SummaryIndividual organ development must be temporally coordinated with development of the rest of the organism. As a result, cell division in a developing organ occurs on a relatively fixed time scale. Despite this, many developing organs can regenerate cells lost to injury. How organs regenerate within the time constraints of organism development remains unclear. Here, we show the developing Drosophila hindgut regenerates by accelerating the mitotic cell cycle. This process requires JAK/STAT signaling and is achieved by decreasing G1 length during the normal period of developmental mitoses. Mitotic capacity is then terminated by the steroid hormone ecdysone receptor. This receptor activates a hindgut-specific enhancer of fizzy-related, a negative regulator of mitotic cyclins. We further identify the Sox transcription factor Dichaete as an important negative regulator of injury-induced mitotic cycles. Our findings reveal how mitotic cell cycle entry mechanisms can be adapted to accomplish developmental organ regeneration.

2012 ◽  
Vol 113 (3) ◽  
pp. 946-955 ◽  
Author(s):  
Estabelle S. M. Ang ◽  
Nathan J. Pavlos ◽  
Shek Man Chim ◽  
Hao Tian Feng ◽  
Robin M. Scaife ◽  
...  

1999 ◽  
Vol 19 (3) ◽  
pp. 2400-2407 ◽  
Author(s):  
Rong Yang ◽  
Carsten Müller ◽  
Vong Huynh ◽  
Yuen K. Fung ◽  
Amy S. Yee ◽  
...  

ABSTRACT Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.


1990 ◽  
Vol 1 (3) ◽  
pp. 315-326 ◽  
Author(s):  
W M Bement ◽  
D G Capco

Transit into interphase of the first mitotic cell cycle in amphibian eggs is a process referred to as activation and is accompanied by an increase in intracellular free calcium [( Ca2+]i), which may be transduced into cytoplasmic events characteristic of interphase by protein kinase C (PKC). To investigate the respective roles of [Ca2+]i and PKC in Xenopus laevis egg activation, the calcium signal was blocked by microinjection of the calcium chelator BAPTA, or the activity of PKC was blocked by PKC inhibitors sphingosine or H7. Eggs were then challenged for activation by treatment with either calcium ionophore A23187 or the PKC activator PMA. BAPTA prevented cortical contraction, cortical granule exocytosis, and cleavage furrow formation in eggs challenged with A23187 but not with PMA. In contrast, sphingosine and H7 inhibited cortical granule exocytosis, cortical contraction, and cleavage furrow formation in eggs challenged with either A23187 or PMA. Measurement of egg [Ca2+]i with calcium-sensitive electrodes demonstrated that PMA treatment does not increase egg [Ca2+]i in BAPTA-injected eggs. Further, PMA does not increase [Ca2+]i in eggs that have not been injected with BAPTA. These results show that PKC acts downstream of the [Ca2+]i increase to induce cytoplasmic events of the first Xenopus mitotic cell cycle.


2000 ◽  
Vol 149 (1) ◽  
pp. 125-140 ◽  
Author(s):  
Andrew Bloecher ◽  
Kelly Tatchell

Protein phosphatase type I (PP1), encoded by the single essential gene GLC7 in Saccharomyces cerevisiae, functions in diverse cellular processes. To identify in vivo subcellular location(s) where these processes take place, we used a functional green fluorescent protein (GFP)–Glc7p fusion protein. Time-lapse fluorescence microscopy revealed GFP–Glc7p localizes predominantly in the nucleus throughout the mitotic cell cycle, with the highest concentrations in the nucleolus. GFP–Glc7p was also observed in a ring at the bud neck, which was dependent upon functional septins. Supporting a role for Glc7p in bud site selection, a glc7-129 mutant displayed a random budding pattern. In α-factor treated cells, GFP–Glc7p was located at the base of mating projections, again in a septin-dependent manner. At the start of anaphase, GFP–Glc7p accumulated at the spindle pole bodies and remained there until cytokinesis. After anaphase, GFP–Glc7p became concentrated in a ring that colocalized with the actomyosin ring. A GFP–Glc7-129 fusion was defective in localizing to the bud neck and SPBs. Together, these results identify sites of Glc7p function and suggest Glc7p activity is regulated through dynamic changes in its location.


Genetics ◽  
1996 ◽  
Vol 144 (3) ◽  
pp. 979-989 ◽  
Author(s):  
Zhixiong Xue ◽  
Xiaoyin Shan ◽  
Alex Sinelnikov ◽  
Teri Melese

Abstract Tetraploid yeast cells lacking BFR1 or overexpressing an essential gene BBPl produce a novel type of ascus that contains asci instead of spores. We show here that the asci within an ascus likely arise because a/α spores undergo a second round of meiosis. Cells depleted of Bbplp or lacking Bfr1p are defective in a number of processes such as nuclear segregation, bud formation, cytokinesis and nuclear spindle formation. Furthermore, deletion of BFR1 or overexpression of BBP1 leads to an increase in cell ploidy, indicating that Bfr1p and Bbplp play roles in both the mitotic cell cycle and meiosis. Bfr1p and Bbp1p interact with each other in a two hybrid assay, further suggesting that they might form a complex important for cell cycle coordination.


1990 ◽  
Vol 10 (12) ◽  
pp. 6356-6361
Author(s):  
M A Drebot ◽  
L M Veinot-Drebot ◽  
R A Singer ◽  
G C Johnston

In the cell cycle of the budding yeast Saccharomyces cerevisiae, expression of the histone genes H2A and H2B of the TRT1 and TRT2 loci is regulated by the performance of "start," the step that also regulates the cell cycle. Here we show that histone production is also subject to an additional form of regulation that is unrelated to the mitotic cell cycle. Expression of histone genes, as assessed by Northern (RNA) analysis, was shown to increase promptly after the stimulation, brought about by fresh medium, that activates stationary-phase cells to reenter the mitotic cell cycle. The use of a yeast mutant that is conditionally blocked in the resumption of proliferation at a step that is not part of the mitotic cell cycle (M.A. Drebot, G.C. Johnston, and R.A. Singer, Proc. Natl. Acad. Sci. 84:7948, 1987) showed that this increased gene expression that occurs upon stimulation of stationary-phase cells took place in the absence of DNA synthesis and without the performance of start. This stimulation-specific gene expression was blocked by the mating pheromone alpha-factor, indicating that alpha-factor directly inhibits expression of these histone genes, independently of start.


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