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Development. 2019 Apr 15;146(8). pii: dev168153. doi: 10.1242/dev.168153.

Lineage context switches the function of a C. elegans Pax6 homolog in determining a neuronal fate.

Author information

1
Skirball Institute of Biomolecular Medicine, Helen L. and Martin S. Kimmel Center for Biology and Medicine, and Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
2
Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
3
Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
4
Skirball Institute of Biomolecular Medicine, Helen L. and Martin S. Kimmel Center for Biology and Medicine, and Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA niels.ringstad@med.nyu.edu.

Abstract

The sensory nervous system of C. elegans comprises cells with varied molecular and functional characteristics, and is, therefore, a powerful model for understanding mechanisms that generate neuronal diversity. We report here that VAB-3, a C. elegans homolog of the homeodomain-containing protein Pax6, has opposing functions in regulating expression of a specific chemosensory fate. A homeodomain-only short isoform of VAB-3 is expressed in BAG chemosensory neurons, where it promotes gene expression and cell function. In other cells, a long isoform of VAB-3, comprising a Paired homology domain and a homeodomain, represses expression of ETS-5, a transcription factor required for expression of BAG fate. Repression of ets-5 requires the Eyes Absent homolog EYA-1 and the Six-class homeodomain protein CEH-32. We determined sequences that mediate high-affinity binding of ETS-5, VAB-3 and CEH-32. The ets-5 locus is enriched for ETS-5-binding sites but lacks sequences that bind VAB-3 and CEH-32, suggesting that these factors do not directly repress ets-5 expression. We propose that a promoter-selection system together with lineage-specific expression of accessory factors allows VAB-3/Pax6 to either promote or repress expression of specific cell fates in a context-dependent manner. This article has an associated 'The people behind the papers' interview.

KEYWORDS:

C. elegans; Chemosensory; Nervous system; VAB-3

PMID:
30890567
DOI:
10.1242/dev.168153

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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