Vestigial-like 3 is a novel Ets1 interacting partner and regulates trigeminal nerve formation and cranial neural crest migration

Abstract

Drosophila Vestigial is the founding member of a protein family containing a highly conserved domain, called Tondu, which mediates their interaction with members of the TEAD family of transcription factors (Scalloped in Drosophila). In Drosophila, the Vestigial/Scalloped complex controls wing development by regulating the expression of target genes through binding to MCAT sequences. In vertebrates, there are four Vestigial-like genes, the functions of which are still not well understood. Here, we describe the regulation and function of vestigial-like 3 (vgll3) during Xenopus early development. A combination of signals, including FGF8, Wnt8a, Hoxa2, Hoxb2 and retinoic acid, limits vgll3 expression to hindbrain rhombomere 2. We show that vgll3 regulates trigeminal placode and nerve formation and is required for normal neural crest development by affecting their migration and adhesion properties. At the molecular level, vgll3 is a potent activator of pax3, zic1, Wnt and FGF, which are important for brain patterning and neural crest cell formation. Vgll3 interacts in the embryo with Tead proteins but unexpectedly with Ets1, with which it is able to stimulate a MCAT driven luciferase reporter gene. Our findings highlight a critical function for vgll3 in vertebrate early development.

Transcription profiles of age-at-maturity-associated genes suggest cell fate commitment regulation as a key factor in the Atlantic salmon maturation process

“…Consistently, vgll3 overexpression is found in sarcomas (23) and cartilage with endemic osteoarthritis (24). During embryonic development (25)(26)(27) and in adult vertebrates (22,25,28,29), the expression of vgll3 has been detected in various tissues, including skeletal muscle, skin, heart, lung, gill, nose, kidney, liver, spleen, stomach, gut, pyloric caeca, brain and eye, potentially suggesting a broad role in development.…”

“…vgll3 expression is also observed in testis (25,29,30) and ovary (29,31), further supporting the participation of Vgll3 in sexual maturation. The exact molecular mechanisms via which Vgll3 operates on cell fate determination, and also maturation, are unclear, but it is known to be a cofactor for all known Tead transcription factors (22,27). By binding to Teads, Vgll3 has been shown to influence the Hippo signaling pathway (22) that regulates cell fate commitment and organ growth (32,33).…”

Transcription Profiles of Age-at-Maturity-Associated Genes Suggest Cell Fate Commitment Regulation as a Key Factor in the Atlantic Salmon Maturation Process

“…Studies show that Vgll3 overexpression promotes expression of the chondrocyte and osteocyte inducing markers in murine preadipocyte cell line (Halperin et al 2013) and myogenesis in mouse and human myoblasts (Figeac et al 2019). Expression pattern of vgll3 during embryonic development (Faucheux et al 2010;Simon et al 2016;Simon et al 2017) and in adult vertebrates (Mielcarek et al 2009;Faucheux et al 2010;Kjaerner-Semb et al 2018;Figeac et al 2019) in various tissues suggests a broad role for Vgll3 in development. Detection of vgll3 expression in testis (Faucheux et al 2010;McDowell et al 2012;Kjaerner-Semb et al 2018) and ovary (Gambaro et al 2013;Kjaerner-Semb et al 2018) further supports the participation of Vgll3 in sexual maturation.…”

“…Detection of vgll3 expression in testis (Faucheux et al 2010;McDowell et al 2012;Kjaerner-Semb et al 2018) and ovary (Gambaro et al 2013;Kjaerner-Semb et al 2018) further supports the participation of Vgll3 in sexual maturation. The exact molecular mechanisms via which VGLL3 operates on cell fate determination, and also maturation, are unclear, but it is known to be a cofactor for all known TEAD transcription factors (Simon et al 2017;Figeac et al 2019). By binding to TEADs, VGLL3 has been shown to influence the Hippo signaling pathway (Figeac et al 2019) that regulates cell fate commitment and organ growth (Huang et al 2005;Meng et al 2016).…”

VGLL3 is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in stomach adenocarcinoma

“…VGLL3 is an inhibitor of adipocyte differentiation and a novel Ets1 interacting partner, and regulates trigeminal nerve formation and cranial neural crest migration 7,22 . In cancer, VGLL3 has been shown to be overexpressed in a subset of soft tissue sarcomas 8 , and was associated with a tumor suppressor phenotype in epithelial ovarian cancer 6 .…”