Higher organisms progress through several discrete developmental stages during their post- embryonic development. The molecular mechanism of these transitions, and the endogenous and environmental factors that influence their timing, are major problems in developmental biology and have important implications for human health. Molecular-genetic analyses of the juvenile-to-adult transition in plants and Caenorhabditis elegans have revealed striking similarities between these processes. In both plants and C. elegans, stage transitions are regulated by a change in the abundance of miRNAs that repress the expression of transcription factors or other key regulatory proteins. However, the molecular basis for this change miRNA levels, and the effect of this change on the expression of the direct targets of these miRNAs are still incompletely understood. In Arabidopsis thaliana, the juvenile-to-adult transition (vegetative phase change) is regulated by a decrease in the expression of two related miRNAs, miR156 and miR157 that promote the expression of the juvenile phase by repressing the expression of SPL transcription factors. The factors responsible for the temporal expression of these miRNAs will be identified using a directed molecular approach and a sensitized genetic screen. To determine the regulatory architecture of the pathway that regulates vegetative phase change, the function of the SPL genes regulated by mir156/miR157 and the ways in which they interact with each other and with MIR156A and MIR156C will be determined by characterizing the developmental and molecular phenotypes of loss-of-function mutations in these genes. The quantitative effect of miR156 on the expression of its direct targets will be measured using protein-reporter constructs. This will reveal if miR156 fine-tunes gene expression, or acts as a thresholding factor to promote alternate developmental states. Finally, the organismal location of the developmental clock that regulates vegetative phase change will be investigated by testing the role of the shoot apical meristem in this process. These experiments will provided detailed information about the molecular mechanism of vegetative phase change in Arabidopsis, and contribute to an improved understanding of the regulation of developmental timing in higher organisms.

Public Health Relevance

Defects in developmental timing underlie many human diseases and inherited disorders. A better understanding of the fundamental mechanism of developmental timing, and the role of miRNAs in this process, is essential for developing therapies for these problems.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM051893-17
Application #
8698429
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Hoodbhoy, Tanya
Project Start
1995-01-01
Project End
2017-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
17
Fiscal Year
2014
Total Cost
$320,392
Indirect Cost
$116,657
Name
University of Pennsylvania
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Yang, Li; Conway, Susan R; Poethig, R Scott (2011) Vegetative phase change is mediated by a leaf-derived signal that represses the transcription of miR156. Development 138:245-9
Wang, Jia-Wei; Park, Mee Yeon; Wang, Ling-Jian et al. (2011) miRNA control of vegetative phase change in trees. PLoS Genet 7:e1002012
Wu, Gang; Park, Mee Yeon; Conway, Susan R et al. (2009) The sequential action of miR156 and miR172 regulates developmental timing in Arabidopsis. Cell 138:750-9
Smith, Michael R; Willmann, Matthew R; Wu, Gang et al. (2009) Cyclophilin 40 is required for microRNA activity in Arabidopsis. Proc Natl Acad Sci U S A 106:5424-9
Yamaguchi, Ayako; Wu, Miin-Feng; Yang, Li et al. (2009) The microRNA-regulated SBP-Box transcription factor SPL3 is a direct upstream activator of LEAFY, FRUITFULL, and APETALA1. Dev Cell 17:268-78
Mlotshwa, Sizolwenkosi; Pruss, Gail J; Peragine, Angela et al. (2008) DICER-LIKE2 plays a primary role in transitive silencing of transgenes in Arabidopsis. PLoS One 3:e1755
Willmann, Matthew R; Poethig, R Scott (2007) Conservation and evolution of miRNA regulatory programs in plant development. Curr Opin Plant Biol 10:503-11
Lu, Cheng; Kulkarni, Karthik; Souret, Frederic F et al. (2006) MicroRNAs and other small RNAs enriched in the Arabidopsis RNA-dependent RNA polymerase-2 mutant. Genome Res 16:1276-88
Wu, Gang; Poethig, R Scott (2006) Temporal regulation of shoot development in Arabidopsis thaliana by miR156 and its target SPL3. Development 133:3539-47

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