FGF/MAPK/Ets signaling renders pigment cell precursors competent to respond to Wnt signal by directly controllingCi-Tcftranscription

Abstract

SUMMARYFGF and Wnt pathways constitute two fundamental signaling cascades, which appear to crosstalk in cooperative or antagonistic fashions in several developmental processes. In vertebrates, both cascades are involved in pigment cell development, but the possible interplay between FGF and Wnt remains to be elucidated. In this study, we have investigated the role of FGF and Wnt signaling in development of the pigment cells in the sensory organs of C. intestinalis. This species possesses the basic features of an ancestral chordate, thus sharing conserved molecular developmental mechanisms with vertebrates. Chemical and targeted perturbation approaches revealed that a FGF signal, spreading in time from early gastrulation to neural tube closure, is responsible for pigment cell precursor induction. This signal is transmitted via the MAPK pathway, which activates the Ci-Ets1/2 transcription factor. Targeted perturbation of Ci-TCF, a downstream factor of the canonical Wnt pathway, indicated its contribution to pigment cell differentiation Furthermore, analyses of the Ci-Tcf regulatory region revealed the involvement of the FGF effector, Ci-Ets1/2, in Ci-Tcf transcriptional regulation in pigment cell precursors. Our results indicate that both FGF and the canonical Wnt pathways are involved in C. intestinalis pigment cell induction and differentiation. Moreover, we present a case of direct transcriptional regulation exerted by the FGF signaling cascade, via the MAPK-ERK-Ets1/2, on the Wnt downstream gene CiTcf. Several examples of FGF/Wnt signaling crosstalk have been described in different developmental processes; however, to our knowledge, FGF-Wnt cross-interaction at the transcriptional level has never been previously reported. These findings further contribute to clarifying the multitude of FGF-Wnt pathway interactions.

Vertebrate Cranial Placodes as Evolutionary Innovations—The Ancestor's Tale

“…While the gene encoding Vent has been lost from the ascidian genome, Msx in ascidians is also expressed in nonneural ectoderm but extends into the lateral neural plate like in vertebrates, where it overlaps with Pax3/7, Snail, Ets, and elevated Zic expression (Corbo, Erives, DiGregorio, Chang, & Levine, 1997;Gostling & Shimeld, 2003;Imai et al, 2004;Ma et al, 1996;Mazet, Hutt, Millard, & Shimeld, 2003;Mazet, Yu, Liberles, Holland, & Shimeld, 2003;Squarzoni, Parveen, Zanetti, Ristoratore, & Spagnuolo, 2011;Wada, Holland, & Satoh, 1996;Wada & Saiga, 2002;. These TFs may help to define a lateral neural plate identity as in vertebrates.…”

Fibroblast growth factor signalling controls nervous system patterning and pigment cell formation in Ciona intestinalis

“…We recently showed that the FGF/MAPK/Ets pathway is responsible for pigmented cell precursor specification, starting from the late gastrula stage, by rendering their progenies competent to respond to a Wnt signal17. However, the FGF signalling downstream targets involved in the regulatory architecture of pigment cell lineage formation remain uncharacterized.…”

The involvement of three signal transduction pathways in botryllid ascidian astogeny, as revealed by expression patterns of representative genes

“…In solitary ascidian species, STP expression and functions during ontogenic stages have been elucidated for Wnt/b-catenin (Niwano et al, 2009;Hudson et al, 2013), TGF-b (Kobayashi et al, 1999;Kobayashi and Makabe, 2001;Hino et al, 2003;Kawashima et al, 2005;Christiaen et al, 2010;Nishide et al, 2012) and MAPK/ ERK (Bertrand et al, 2003;Hudson et al, 2003;Nishida, 2003;Pasini et al, 2006;Chambon et al, 2007;Sakabe et al, 2006) pathways alone, or in combination with other STPs (Hudson et al, 2007;Lemaire, 2009;Pasini et al, 2012;Sasakura et al, 2012;Squarzoni et al, 2011). This has not been extensively studied in colonial species where astogenic and ontogenic pathways are developing side by side and in concert.…”