Aug 5, 2019
Unlocking the secrets of an important regulator of human development
Mar 26, 2019
Über die Pubertät weiss man jetzt mehr – dank einem winzigen Wurm
Mar 25, 2019
A key player in the maturation of sexual organs
May 3, 2018
Cracking the RNA-binding code of a cell fate regulator
Mar 23, 2018
Breakthrough article on mechanistic features of microRNA targeting and activity
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Biological clocks and timers in development
The development of an animal requires proper temporal synchronization of diverse events, facilitated by developmental clocks. How such clocks function is only beginning to emerge. What are their properties? What are the components that make them run, and how are they wired? To solve these questions, we investigate developmental timing in the roundworm C. elegans, where we can exploit our recent discovery that thousands of genes oscillate in expression during larval development. Such extensive and robust molecular clock output, combined with powerful tools for genetic manipulation and screening, makes C. elegans uniquely suited for dissecting the underlying clock mechanism. We combine high-throughput single animal-based methods including quantitative time-lapse imaging with genomics, genetic and computational approaches to record and alter oscillations and developmental timing. Thus, we aim to establish a mechanistic and quantitative model of the clock.
Although oscillator-based developmental clocks are crucial to control execution of repetitive events such as the formation of vertebrae in mammals, distinct mechanisms time linear progression. For instance, transition from juvenile (larval) to adult fates in C. elegans relies on a regulatory cascade, where an RNA-binding protein, LIN28, represses a miRNA, let-7, which in turn represses another RNA-binding protein, LIN41/TRIM71. The functions of these factors appear conserved in mammals where they regulate stem cell fates and, possibly, the onset of puberty. Working with C. elegans and mammalian cells, we aim to obtain a full mechanistic understanding of this pathway and its components to understand how control of 'linear time' is achieved and integrated with clock-controlled processes.
This is a list of selected publications from this group. For a full list of publications, please visit our Publications page and search by group name.
Aeschimann, F., Neagu, A., Rausch, M., and Grosshans, H. (2019) A single let-7 target to coordinate transition to adulthoodLife Science Alliance 2, e201900335
Pereira, L., Aeschimann, F., Wang, C., Lawson, H., Serrano-Saiz, E., Portman, D.S., Grosshans, H., Hobert, O. (2019) Timing mechanism of sexually dimorphic nervous system differentiationeLIFE 8: e42078.
Kumari, P.*, Aeschimann, F.*, Gaidatzis, D.*, Keusch, J.J.*, Ghosh, P., Neagu, A., Pachulska-Wieczorek, K., Bujnicki, J.M., Gut, H., Grosshans, H., Ciosk, R. (2018) Evolutionary plasticity of the NHL domain underlies distinct solutions to RNA recognitionNat. Commun. 9: 1549
* Equal contribution
Brancati, G., and Grosshans, H. (2018) An interplay of miRNA abundance and target site architecture determines miRNA activity and specificityNucleic Acids Res. 46: 3259-3269
Miki TS, Carl SH, Grosshans H (2017) Two distinct transcription termination modes dictated by promotersGenes Dev. 31: 1870-1879.
Aeschimann F, Kumari P, Bartake H, Gaidatzis D, Xu L, Ciosk R, Grosshans H (2017) LIN41 post-transcriptionally silences mRNAs by two distinct and position-dependent mechanismsMol Cell 65:476-489.
Richter H, Katic I, Gut H, Grosshans H (2016) Structural basis and function of XRN2 binding by XTB domainsNat Struct Mol Biol 23:164-71
de la Mata M, Gaidatzis D, Vitanescu M, Stadler MB, Wentzel C, Scheiffele P, Filipowicz W, Grosshans H (2015) Potent degradation of neuronal miRNAs induced by highly complementary targetsEMBO Rep 16:500-11
Ecsedi M, Rausch M Grosshans H (2015) The let-7 microRNA directs vulval development through a single targetDev Cell 32:335-44
Hendriks GJ, Gaidatzis D, Aeschimann F, Grosshans H (2014) Extensive oscillatory gene expression during C. elegans larval developmentMol Cell 53:380-92.
Katic I, Grosshans H (2013) Targeted heritable mutation and gene conversion by Cas9-CRISPR in Caenorhabditis elegansGenetics 195:1173-6
Chatterjee S, Fasler M, Büssing I, Grosshans H (2011) Target-mediated protection of endogenous microRNAs in C. elegansDev Cell 20:388-396
Büssing I, Yang J-S, Lai EC, Grosshans H (2010) The nuclear export receptor XPO-1 supports primary miRNA processing in C. elegans and Drosophila.EMBO J 29:1830-1839
Chatterjee S, Grosshans H (2009) Active turnover modulates mature microRNA activity in C. elegansNature 461:546-549
Ding XC, Grosshans H (2009) Repression of C. elegans microRNA targets at the initiation level of translation requires GW182 proteinsEMBO J 28:213-222
Full list of publications
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