lin-3

We have shown that lin-3 is also expressed in the 1 degrees vulval lineage after vulval induction and that the 1 degrees vulva is necessary to induce the uv1 uterine cell fate.

In neurons, LET-23 functioned at the upstream of DAF-7/DBL-1, ligands of TGF-β signals, to mediate PS-A NPs' transgenerational toxicity.

Correlation of mutant phenotypes and their molecular lesions, as well as sequence comparison between two species, reveal that the EGF motif and the N-terminal portion of the cytoplasmic domain are important for the functions of LIN-3 in all tissues, while the C-terminal portion of the cytoplasmic domain is involved in the tissue-specific functions of lin-3.

In the uterus, lin-29 functioned upstream of lin-12 in the induction of pi cells and was necessary to maintain expression in the AC of lag-2, which encodes a ligand for LIN-12.

We identify a class A synMuv mutation in the promoter of the lin-3 EGF gene, establishing that lin-3 is the key biological target of the class A synMuv genes in vulval development and that the repressive activities of the class A and B synMuv pathways are integrated at the level of lin-3 expression.

The ectodomain of SISS-1 , but not of LIN-3 , also contains an Immunoglobulin-like (Ig) domain, putting it into a class of Ig-EGFs that includes Drosophila Vein and certain vertebrate Neuregulins.

Moreover, endogenous MIG-15 is required for expression of a fluorescent biomarker of 3˚ cell fate, is expressed in VPCs, and functions cell autonomously in VPCs.

LET-23 acted at the upstream DAF-16/FOXO within the intestine in response to PS-A NPs' transgenerational toxicity.

The C. elegans lin-3 gene encodes an epidermal growth factor family (EGF) growth factor. lin-3 is expressed in the gonadal anchor cell and acts through LET-23 (transmembrane protein tyrosine kinase and ortholog of EGF receptor) to signal the vulval precursor cells to generate vulval tissue. lin-3 is expressed in the vulval cells later, and recent evidence raises the possibility that lin-3 acts in the vulval cells as a relay signal during vulval induction.

The C. elegans lin-3 gene encodes an epidermal growth factor family (EGF) growth factor. lin-3 is expressed in the gonadal anchor cell and acts through LET-23 (transmembrane protein tyrosine kinase and ortholog of EGF receptor) to signal the vulval precursor cells to generate vulval tissue. lin-3 is expressed in the vulval cells later, and recent evidence raises the possibility that lin-3 acts in the vulval cells as a relay signal during vulval induction.

We find that lin-15 acts upstream of let-23 and in parallel to the inductive signal.

Expression of lin-3 in the anchor cell stimulates vulval induction; lin-3 may encode the vulval inducing signal.

These results suggest hypotheses for the mechanistic basis of the functional redundancy between the tumor-suppressor-like class A and B synMuv genes: the class A synMuv genes either directly or indirectly specifically repress ectopic lin-3 expression; while the class B synMuv genes might function similarly, but alternatively might act to repress lin-3 as a consequence of their role in preventing cells from adopting a germline-like fate.

These results suggest a cross-talk between nutrient deprivation, TOR-S6K and EGF-Ras-MAPK signaling during C. elegans vulval induction.

Using FISH with single mRNA molecule resolution, we find that lin-3 EGF expression is tightly restricted to only a few tissues in wild-type animals, including the germline.

To determine if IGEG-2 is a functional EGFR ligand, we examined whether it can activate known LET-23-dependent processes.

We demonstrate that lin-15 acts in spicule development as it does in vulval induction, as a negative regulator of let-23 receptor activity.

Using the strong starvation suppression of the Vulvaless phenotype of lin-3/egf reduction-of-function mutations as an experimental paradigm, we first tested for a possible involvement of the sensory system in relaying starvation signals to affect vulval induction: mutation of various sensory inputs, DAF-2/Insulin or DAF-7/TGF-β signaling did not abolish lin-3(rf) starvation suppression.

However, this signal is apparently integrated into the lin-3/let-23 pathway at some step after lin-45 raf and is thus functionally distinct from lin-15.

We show that LIN-3 is an inductive signal sufficient to promote the P12 fate, and the conserved EGF signaling pathway is utilized for P12 fate specification; egl-5 is a downstream target of the lin-3/let-23 pathway in specifying P12 fate; and LIN-44 and LIN-17 act synergistically with lin-3 in the specification of the P12 fate.