A gene network that coordinates preplacodal competence and neural crest specification in zebrafish

Abstract

Preplacodal ectoderm (PPE) and neural crest (NC) are specified at the interface of neural and nonneural ectoderm and together contribute to the peripheral nervous system in all vertebrates. Bmp activates early steps for both fates during late blastula stage. Low Bmp activates expression of transcription factors Tfap2a and Tfap2c in the lateral neural plate, thereby specifying neural crest fate. Elevated Bmp establishes preplacodal competence throughout the ventral ectoderm by coinducing Tfap2a, Tfap2c, Foxi1 and Gata3. PPE specification occurs later at the end of gastrulation and requires complete attenuation of Bmp, yet expression of PPE competence factors continues well past gastrulation. Here we show that competence factors positively regulate each other’s expression during gastrulation, forming a self-sustaining network that operates independently of Bmp. Misexpression of Tfap2a in embryos blocked for Bmp from late blastula stage can restore development of both PPE and NC. However, Tfap2a alone is not sufficient to activate any other competence factors nor does it rescue individual placodes. On the other hand, misexpression of any two competence factors in Bmp-blocked embryos can activate the entire transcription factor network and support the development of NC, PPE and some individual placodes. We also show that while these factors are partially redundant with respect to PPE specification, they later provide non-redundant functions needed for development of specific placodes. Thus, we have identified a gene regulatory network that coordinates development of NC, PPE and individual placodes in zebrafish.

Establishing neural crest identity: a gene regulatory recipe

“…Studies in multiple vertebrates have shown that, once their expression commences in the neural plate border region, these transcription factors engage in a series of mutual cross-regulatory interactions that lead to the stabilization of this regulatory state (Fig. 3C) and ensure their continued expression (Monsoro-Burq et al, 2005;Sato et al, 2005;Nikitina et al, 2008;Bhat et al, 2013).…”

“…For instance, Nikitina and colleagues showed that Tfap2a and Msx1 activate not only each other, but also Zic1 and Pax3/7 (Nikitina et al, 2008). Tfap2a seems to be a key activator of neural plate border specifiers, also being required for the expression of Foxi genes and gata2/3 in zebrafish (Bhat et al, 2013). The more lateral neural plate border genes (Dlx5/6, Gata2/3 and Foxi1/3) also positively regulate each other in multiple positive regulatory loops (McLarren et al, 2003;Matsuo-Takasaki et al, 2005;Kwon et al, 2010; reviewed by Grocott et al, 2012).…”

Zebrafish Wnt9b Patterns the First Pharyngeal Arch into D-I-V Domains and Promotes Anterior-Medial Outgrowth

“…The oral ectoderm, which is the presumptive primary mouth, is specified very early and develops from the most anterior portion of a horseshoe shaped preplacodal ectoderm (PPE) [59] [60]. The preplacodal ectoderm region subsequently divides into multiple subdomains, becoming the single oral, and the bilateral nasal, optic, and otic cranial sensory placodes [61].…”

Mechanisms of cranial placode assembly

“…The formation of segregated placode primordia correlates in time with upregulation of transcription factors specifically expressed in individual or groups of placodes Pieper et al, 2011;Schlosser, 2010;Streit, 2008). Pax2 and Pax8, expressed in the otic and epibranchial placode progenitors (and in lateral line placodes in fish and amphibians), show saltand-pepper expression in chick (Groves and Bronner-Fraser, 2000;Streit, 2002), Xenopus (Pieper et al, 2011;Schlosser and Ahrens, 2004), zebrafish (Bhat et al, 2013;Bhat and Riley, 2011;Hans and Westerfield, 2007;McCarroll et al, 2012; Kozlowski et al, 1997;Bhattacharyya and Bronner, 2013;Breau et al, 2012;Dutta et al, 2005;Harden et al, 2012;Knaut et al, 2005;Kwan et al, 2011;Pieper et al, 2011;Streit, 2002;Whitlock and Westerfield, 2000;Xu et al, 2008) al., 2012) and mice (Ohyama and Groves, 2004). Pax6, a transcription factor expressed in the lens placode, exhibit mosaic expression in zebrafish (Dutta et al, 2005;Hans and Westerfield, 2007).…”