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

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;2(3). pii: e201800255. doi: 10.26508/lsa.201800255. Print 2019 Jun.

PMID: 3112699 4Free PMC Article

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;13(1):e1006592.

doi: 10.1371/journal.pgen.1006592. 2017 Jan.

PMID: 28135265 Free PMC Article

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;11(5):e1005236.

doi: 10.1371/journal.pgen.1005236. eCollection 2015 May.

PMID: 25978500 Free PMC Article

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.