Abstract:Melanocytes derive from neural crest cells, which are a highly migratory population of cells that play an important role in pigmentation of the skin and epidermal appendages. In most vertebrates, melanocyte precursor cells migrate solely along the dorsolateral pathway to populate the skin. However, zebrafish melanocyte precursors also migrate along the ventromedial pathway, in route to the yolk, where they interact with other neural crest derivative populations. Here, we demonstrate the requirement for zebrafi… Show more
“…10.7554/eLife.45181.014Figure 3—figure supplement 4.Genes identified as zebrafish pigmentation mutants often had expression domains beyond affected cell types.Mutations affecting a variety of pigmentary traits have been recovered or induced and affect pigment deposition, specification or morphogenesis of one or more pigment cell classes, and pattern at EL, adult or both stages (Arduini et al, 2009; Barrallo-Gimeno et al, 2004; Beirl et al, 2014; Budi et al, 2008; D'Agati et al, 2017; Dooley et al, 2013b; Dutton et al, 2001; Eskova et al, 2017; Fadeev et al, 2015; Inoue et al, 2014; Irion et al, 2014; Iwashita et al, 2006; Knight et al, 2003; Krauss et al, 2013; Larson et al, 2010; Nagao et al, 2018; Parichy et al, 2000a; Sheets et al, 2007; Watanabe et al, 2006; Williams et al, 2018; Zhang et al, 2018). Shown are expression domains observed for affected genes in scRNA-Seq analyses of adult NC-derived cells (euthyroid and hypothyroid).…”
Thyroid hormone (TH) regulates diverse developmental events and can drive disparate cellular outcomes. In zebrafish, TH has opposite effects on neural crest derived pigment cells of the adult stripe pattern, limiting melanophore population expansion, yet increasing yellow/orange xanthophore numbers. To learn how TH elicits seemingly opposite responses in cells having a common embryological origin, we analyzed individual transcriptomes from thousands of neural crest-derived cells, reconstructed developmental trajectories, identified pigment cell-lineage specific responses to TH, and assessed roles for TH receptors. We show that TH promotes maturation of both cell types but in distinct ways. In melanophores, TH drives terminal differentiation, limiting final cell numbers. In xanthophores, TH promotes accumulation of orange carotenoids, making the cells visible. TH receptors act primarily to repress these programs when TH is limiting. Our findings show how a single endocrine factor integrates very different cellular activities during the generation of adult form.
“…10.7554/eLife.45181.014Figure 3—figure supplement 4.Genes identified as zebrafish pigmentation mutants often had expression domains beyond affected cell types.Mutations affecting a variety of pigmentary traits have been recovered or induced and affect pigment deposition, specification or morphogenesis of one or more pigment cell classes, and pattern at EL, adult or both stages (Arduini et al, 2009; Barrallo-Gimeno et al, 2004; Beirl et al, 2014; Budi et al, 2008; D'Agati et al, 2017; Dooley et al, 2013b; Dutton et al, 2001; Eskova et al, 2017; Fadeev et al, 2015; Inoue et al, 2014; Irion et al, 2014; Iwashita et al, 2006; Knight et al, 2003; Krauss et al, 2013; Larson et al, 2010; Nagao et al, 2018; Parichy et al, 2000a; Sheets et al, 2007; Watanabe et al, 2006; Williams et al, 2018; Zhang et al, 2018). Shown are expression domains observed for affected genes in scRNA-Seq analyses of adult NC-derived cells (euthyroid and hypothyroid).…”
Thyroid hormone (TH) regulates diverse developmental events and can drive disparate cellular outcomes. In zebrafish, TH has opposite effects on neural crest derived pigment cells of the adult stripe pattern, limiting melanophore population expansion, yet increasing yellow/orange xanthophore numbers. To learn how TH elicits seemingly opposite responses in cells having a common embryological origin, we analyzed individual transcriptomes from thousands of neural crest-derived cells, reconstructed developmental trajectories, identified pigment cell-lineage specific responses to TH, and assessed roles for TH receptors. We show that TH promotes maturation of both cell types but in distinct ways. In melanophores, TH drives terminal differentiation, limiting final cell numbers. In xanthophores, TH promotes accumulation of orange carotenoids, making the cells visible. TH receptors act primarily to repress these programs when TH is limiting. Our findings show how a single endocrine factor integrates very different cellular activities during the generation of adult form.
“…1K). Zebrafish mutant alleles can trigger “transcriptional adaptation”, whereby NMD-produced fragments trigger upregulation of related genes that replace lost gene function (El-Brolosy et al, 2019; El-Brolosy & Stainier, 2017; Rossi et al, 2015; Williams et al, 2018). However, neither ezh1 nor ezh2 alleles produced compensatory expression of the corollary transcript (Fig.…”
Polycomb repressive complex-2 (PRC2) methylation of histone H3 lysine-27 (H3K27me) is associated with stable transcriptional repression. PRC2 famously silences Hox genes to maintain anterior-posterior segment identities but also enables early cell fate specification, restrains progenitor cell differentiation, and canalizes cell identities. Zebrafish PRC2 genetic studies have focused on ezh2, which, with its paralog ezh1, encodes the H3K27 methyltransferase component. ezh2 loss-of-function mutants reinforce essential vertebrate PRC2 functions during early embryogenesis albeit with limited contributions to body plan establishment. However, redundancy with ezh1 and the lethality of maternal-zygotic homozygous ezh2 nulls could obscure additional early developmental and organogenesis roles of PRC2. Here, we combine new and existing zebrafish ezh1 and ezh2 alleles to show collective maternal/zygotic ezh2 exclusively provides earliest embryonic PRC2 H3K27me3 activity. Zygotic ezh1, which becomes progressively expressed as ezh2 levels dissipate, has minor redundant and noncompensatory larval roles but itself is not required for viability or fertility. Zygotic Ezh2/PRC2 promotes correct craniofacial bone shape and size by maintaining proliferative pre-osteoblast pools. An ezh2 allelic series including disrupted maternal ezh2 uncovers axial skeleton homeotic transformations and pleiotropic organogenesis defects. Further, once past a critical early window, we show zebrafish can develop near normally with minimal bulk H3K27me3. Our results suggest Ezh2-containing PRC2 stabilizes rather than instructs early developmental decisions while broadly contributing to organ size and embellishment.
“…Protocadherins like PCDH10A and PCDHAC2 are essential to fish skin patterning (e.g. Kelsh et al, 2009, Williams, Hsu, Rossi, & Artinger, 2018; Du et al, 2019).…”
Colour and pigmentation variation attracted fish biologists for a while, but high-throughput genomic studies investigating the molecular basis of body pigmentation remain still limited to few species and conservation biology issues ignored. Using 75,684 SNPs, we investigated the genomic basis of pigmentation pattern variation among individuals of the Atlantic and Mediterranean clades of the brown trout (Salmo trutta), a polytypic species in which Atlantic hatchery individuals are commonly used to supplement local wild populations. Using redundancy analyses and genome-wide association studies, a set of 384 “colour patterning loci” (CPL) significantly correlated with pigmentation traits such as the number of red and black spots on flanks, but also the presence of a large black stain on the opercular bone was identified. CPLs map onto 35 out of 40 brown trout linkage groups indicating a polygenic basis to pigmentation patterns. They are mostly located in coding regions (43.4%) of 223 candidate genes, and correspond to GO-terms known to be involved in pigmentation (e.g. calcium and ion-binding, cell adhesion). Annotated genes especially include 24 candidates with known pigmentation effects (e.g. SOX10, PEML, SLC45A2), but also the Gap-junction Δ2 (GJD2) gene that was previously showed be differentially expressed in trout skin. Patterns of admixture were found significantly distinct when using either the full SNP data set or the set of CPLs, indicating that pigmentation patterns accessible to practitioners are not a reliable proxy of genome-wide admixture. Consequences for management are discussed.
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