EGFR/RAS/MAPK signaling during Caenorhabditis elegans development

We are investigating the different roles the conserved EGFR/RAS/MAPK signaling pathway plays during the development of two different organs in Caenorhabditis elegans. The first organ, the vulva of the hermaphrodite, is a paradigm model to study how the combined action of the evolutionary conserved EGFR/RAS/MAPK, WNT and NOTCH signaling pathways determines an invariant pattern of cell fates during organogenesis, leading to the formation of a simple organ consisting of 22 cells. In the second organ, the hermaphrodite gonad, we are investigating the differentiation of the germ cells. Germ cell proliferation and differentiation are also controlled by the NOTCH and RAS/MAPK signaling pathways, but in contrast to the vulva, the germ cells do not follow a fixed cell lineage. Approximately half of the germ cells in meiotic prophase I are eliminated through apoptosis. The decision whether a germ cell enters oogenesis or undergoes apoptosis is made in a stochastic manner. Germ cell development thus serves as a model to study cell homeostasis in a self-renewing organ.

Loss of EGFR results in vulvaless worms (GIF, 10 MB)

Loss of EGFR results in vulvaless worms

Enhanced EGFR/RAS/MAPK signaling leads to the formation of multiple vulvae (GIF, 15 MB)

Enhanced EGFR/RAS/MAPK signaling leads to the formation of multiple vulvae

Key publications

Nutritional vitamin B12 regulates RAS/MAPK-mediated cell fate decisions through one-carbon metabolism

Laranjeira AC, Berger S, Kohlbrenner T, Greter NR, Hajnal A.
Nat Commun. 2024 Sep 18

Reciprocal EGFR signaling in the anchor cell ensures precise inter-organ connection during Caenorhabditis elegans vulval morphogenesis.

Spiri S, Berger S, Mereu L, DeMello A, Hajnal A.
Development. 2022 Jan 1

Polarized epidermal growth factor secretion ensures robust vulval cell fate specification in Caenorhabditis elegans

Mereu L, Morf MK, Spiri S, Gutierrez P, Escobar-Restrepo JM, Daube M, Walser M, Hajnal A.
Development. 2020 Jun 4

The hypoxia-response pathway modulates RAS/MAPK-mediated cell fate decisions in Caenorhabditis elegans

Maxeiner S, Grolleman J, Schmid T, Kammenga J, Hajnal A.
Life Alliance. 2019 May 24

β-Integrin de-phosphorylation by the Density-Enhanced Phosphatase DEP-1 attenuates EGFR signaling in C. elegans.

Walser M, Umbricht CA, Fröhli E, Nanni P, Hajnal A.
PLoS Genet. 2017 Jan 30

Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA. Schmid T, Snoek LB, Fröhli E, van der Bent ML, Kammenga J, Hajnal A.
PLoS Genet. 2015 May 15

An in vivo EGF receptor localization screen in C. elegans Identifies the Ezrin homolog ERM-1 as a temporal regulator of signaling.

Haag A, Gutierrez P, Bühler A, Walser M, Yang Q, Langouët M, Kradolfer D, Fröhli E, Herrmann CJ, Hajnal A, Escobar-Restrepo JM.
PLoS Genet. 2014 May 1

PTEN negatively regulates MAPK signaling during Caenorhabditis elegans vulval development.

Nakdimon I, Walser M, Fröhli E, Hajnal A.
Genet. 2012 Aug 16.

Cell fate-specific regulation of EGF receptor trafficking during Caenorhabditis elegans vulval development.

Stetak A, Hoier EF, Croce A, Cassata G, Di Fiore PP, Hajnal A.
EMBO J. 2006 Jun 7

The C. elegans homolog of the mammalian tumor suppressor Dep-1/Scc1 inhibits EGFR signaling to regulate binary cell fate decisions.

Berset TA, Hoier EF, Hajnal A.
Genes Dev. 2005 Jun 1

EGF signal propagation during C. elegans vulval development mediated by ROM-1 rhomboid.

Dutt A, Canevascini S, Froehli-Hoier E, Hajnal A.
PLoS Biol. 2004 Nov 

The C. elegans G-protein-coupled receptor SRA-13 inhibits RAS/MAPK signalling during olfaction and vulval development.

Battu G, Hoier EF, Hajnal A.
Development. 2003 Jun

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