A branched heterochronic pathway regulates the juvenile-to-adult transition in Caenorhabditis elegans

Azzi, Chiara. A branched heterochronic pathway regulates the juvenile-to-adult transition in Caenorhabditis elegans. 2022, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: https://edoc.unibas.ch/88843/

Downloads: Statistics Overview


Temporal coordination of disparate events is a hallmark of robust organismal development and dedicated genetically encoded mechanisms enable such temporal control. In Caenorhabditis elegans, the so-called heterochronic pathway times the onset of juvenile-to-adult (J/A) transition, a highly regulated developmental event that involves coordinated behavior of epidermal cells. According to current models, a linear chain of events triggers the J/A transition: accumulation of the let-7 miRNA causes silencing of its direct target LIN-41. This enables the accumulation of the transcription factor LIN-29 and consequently the coordinated execution of J/A transition events. However, several reports challenge this simple model. For this reason, we aim to understand how the heterochronic pathway coordinates the execution of the J/A transition.
In this work, we first revisited the architecture of the heterochronic pathway. We found that two LIN-29 isoforms, LIN-29a and LIN-29b, have distinct functions and regulation. Unique functions are not the result of molecular differences but of distinct spatiotemporal expression patterns of the isoforms, generated by the activity of distinct upstream heterochronic genes. Specifically, we identify LIN-41, an RNA-binding protein, and HBL-1, a transcription factor, to shape lin-29 expression in an isoform-specific manner. While lin-29a is under direct translation control by LIN-41, lin-29b is either directly or indirectly repressed by HBL-1. Coordination of the activities of LIN-29a and LIN-29b is achieved through LIN-28, an upstream heterochronic gene that regulates both LIN-41 and HBL-1. Thereby, our data demonstrate that coordinated J/A transition involves a branched pathway to achieve timely control of multiple events.
Secondly, hbl-1 is an important but poorly described heterochronic gene. Our characterization of the HBL-1-LIN-29b parallel arm of the heterochronic pathway suggests that the transcription factor HBL-1 behaves as a core player of this pathway. We propose that further research on hbl-1 targets and functions will be crucial for a proper understanding of how the heterochronic pathway establishes temporal patterning.
In conclusion, the findings presented in this work provides insight into the architecture, properties and mechanism of a biological timer that temporally controls events occurring during the transition from a juvenile to an adult animal.
Advisors:Grosshans, Helge and Schübeler, Dirk and Cochella, Luisa
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI > Epigenetics > Biological clocks and timers in development (Grosshans)
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:14758
Thesis status:Complete
Number of Pages:103
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss147588
edoc DOI:
Last Modified:21 Jul 2022 08:31
Deposited On:21 Jul 2022 08:31

Repository Staff Only: item control page