A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms

Robust organismal development relies on temporal coordination of disparate physiological processes. In Caenorhabditis elegans, the heterochronic pathway controls a timely juvenile-to-adult (J/A) transition. This regulatory cascade of conserved proteins and small RNAs culminates in accumulation of th...

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Main Authors: Chiara Azzi, Florian Aeschimann, Anca Neagu, Helge Großhans
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/53387
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author Chiara Azzi
Florian Aeschimann
Anca Neagu
Helge Großhans
author_facet Chiara Azzi
Florian Aeschimann
Anca Neagu
Helge Großhans
author_sort Chiara Azzi
collection DOAJ
description Robust organismal development relies on temporal coordination of disparate physiological processes. In Caenorhabditis elegans, the heterochronic pathway controls a timely juvenile-to-adult (J/A) transition. This regulatory cascade of conserved proteins and small RNAs culminates in accumulation of the transcription factor LIN-29, which triggers coordinated execution of transition events. We report that two LIN-29 isoforms fulfill distinct functions. Functional specialization is a consequence of distinct isoform expression patterns, not protein sequence, and we propose that distinct LIN-29 dose sensitivities of the individual J/A transition events help to ensure their temporal ordering. We demonstrate that unique isoform expression patterns are generated by the activities of LIN-41 for lin-29a, and of HBL-1 for lin-29b, whereas the RNA-binding protein LIN-28 coordinates LIN-29 isoform activity, in part by regulating both hbl-1 and lin-41. Our findings reveal that coordinated transition from juvenile to adult involves branching of a linear pathway to achieve timely control of multiple events.
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spelling doaj.art-bc20a89d37f64b3cb0f6c11a9a7b0db02022-12-22T03:33:27ZengeLife Sciences Publications LtdeLife2050-084X2020-03-01910.7554/eLife.53387A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoformsChiara Azzi0https://orcid.org/0000-0002-2240-4618Florian Aeschimann1https://orcid.org/0000-0001-5213-034XAnca Neagu2https://orcid.org/0000-0002-0643-5238Helge Großhans3https://orcid.org/0000-0002-8169-6905Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; University of Basel, Basel, SwitzerlandFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland; University of Basel, Basel, SwitzerlandFriedrich Miescher Institute for Biomedical Research, Basel, SwitzerlandFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland; University of Basel, Basel, SwitzerlandRobust organismal development relies on temporal coordination of disparate physiological processes. In Caenorhabditis elegans, the heterochronic pathway controls a timely juvenile-to-adult (J/A) transition. This regulatory cascade of conserved proteins and small RNAs culminates in accumulation of the transcription factor LIN-29, which triggers coordinated execution of transition events. We report that two LIN-29 isoforms fulfill distinct functions. Functional specialization is a consequence of distinct isoform expression patterns, not protein sequence, and we propose that distinct LIN-29 dose sensitivities of the individual J/A transition events help to ensure their temporal ordering. We demonstrate that unique isoform expression patterns are generated by the activities of LIN-41 for lin-29a, and of HBL-1 for lin-29b, whereas the RNA-binding protein LIN-28 coordinates LIN-29 isoform activity, in part by regulating both hbl-1 and lin-41. Our findings reveal that coordinated transition from juvenile to adult involves branching of a linear pathway to achieve timely control of multiple events.https://elifesciences.org/articles/53387developmental timingterminal differentiationheterochronicpubertymoltepidermis
spellingShingle Chiara Azzi
Florian Aeschimann
Anca Neagu
Helge Großhans
A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms
eLife
developmental timing
terminal differentiation
heterochronic
puberty
molt
epidermis
title A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms
title_full A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms
title_fullStr A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms
title_full_unstemmed A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms
title_short A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms
title_sort branched heterochronic pathway directs juvenile to adult transition through two lin 29 isoforms
topic developmental timing
terminal differentiation
heterochronic
puberty
molt
epidermis
url https://elifesciences.org/articles/53387
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