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

Emilie Simon,Sandrine Fédou,Corinne Faucheux,Nadine Thézé,Pierre Thiébaud

doi:10.1242/bio.026153

Emilie Simon, Sandrine Fédou + Show 3 more

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https://doi.org/10.1242/bio.026153

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Abstract

ABSTRACTDrosophila 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.

Highlights

The vestigial-like (VGLL) family of proteins takes its name from the Drosophila Vestigial (Vg), which is required for the wing formation (Halder et al, 1998; Kim et al, 1996)
Drosophila Vestigial is the founding member of a protein family containing a highly conserved domain, called Tondu that mediates their interaction with members of the TEAD family of transcription factors (Scalloped in Drosophila)
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

Summary

Introduction

The vestigial-like (VGLL) family of proteins takes its name from the Drosophila Vestigial (Vg), which is required for the wing formation (Halder et al, 1998; Kim et al, 1996). Vestigial forms a co-transcriptional activator complex with the protein Scalloped (Sd), a member of the TEAD family of transcription factors, that activates genes involved in wing morphogenesis (Guss et al, 2001). Several Vestigial-like genes have been identified in vertebrates, all encode proteins with a Tondu domain that mediates interaction with TEADs (Bonnet et al, 2010; Chen et al, 2004; Faucheux et al, 2010; Maeda et al, 2002; Mielcarek et al, 2002; Mielcarek et al, 2009; Simon et al, 2016). Mammalian VGLL2 is an essential cofactor of TEAD being able to stimulate muscle differentiation and in zebrafish embryo it is involved in the development of the neural crest cell-derived craniofacial skeleton (Gunther et al, 2004; Johnson et al, 2011; Maeda et al 2002). Mammalian VGLL4 acts, like its Drosophila homolog Tgi, as a repressor of the Hippo pathway (Chen et al, 2004; Guo et al, 2013; Koontz et al, 2013)

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