Selective breeding modifies mef2ca mutant incomplete penetrance by tuning the opposing Notch pathway

Sucharov, Juliana; Ray, Kuval; Brooks, Elliott P.; Nichols, James T.

doi:10.1371/journal.pgen.1008507

Cited by 15 publications

(47 citation statements)

References 69 publications

(100 reference statements)

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“…We interpret the full fusions as being the more severe disruptions (higher expressivity). The variable penetrance and expressivity we observe within the same genetic background are consistent with our previous studies focused on phenotype variability of another craniofacial mutant (DeLaurier et al ., 2014; Nichols et al ., 2016; Sucharov et al ., 2019).…”

Section: Introductionmentioning

confidence: 99%

Transgene‐mediated skeletal phenotypic variation in zebrafish

Kimmel

Wind

Oliva

et al. 2020

Journal of Fish Biology

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When considering relationships between genotype and phenotype we frequently ignore the fact that the genome of a typical animal, notably including that of a fish and a human, harbours a huge amount of foreign DNA. Such DNA, in the form of transposable elements, can affect genome function in a major way, and transgene biology needs to be included in our understanding of the genome. Here we examine an unexpected phenotypic effect of the chromosomally integrated transgene fli1a‐F‐hsp70l:Gal4VP16 that serves as a model for transgene function generally. We examine larval fras1 mutant zebrafish (Danio rerio). Gal4VP16 is a potent transcriptional activator that is already well known for toxicity and mediating unusual transcriptional effects. In the presence of the transgene, phenotypes in the neural crest‐derived craniofacial skeleton, notably fusions and shape changes associated with loss of function fras1 mutations, are made more severe, as we quantify by scoring phenotypic penetrance, the fraction of mutants expressing the trait. A very interesting feature is that the enhancements are highly specific for fras1 mutant phenotypes, occurring in the apparent absence of more widespread changes. Except for the features due to the fras1 mutation, the transgene‐bearing larvae appear generally healthy and to be developing normally. The transgene behaves as a genetic partial dominant: a single copy is sufficient for the enhancements, yet, for some traits, two copies may exert a stronger effect. We made new strains bearing independent insertions of the fli1a‐F‐hsp70l:Gal4VP16 transgene in new locations in the genome, and observed increased severities of the same phenotypes as observed for the original insertion. This finding suggests that sequences within the transgene, for example Gal4VP16, are responsible for the enhancements, rather than the effect on neighbouring host sequences (such as an insertional mutation). The specificity and biological action underlying the traits are subjects of considerable interest for further investigation, as we discuss. Our findings show that work with transgenes needs to be undertaken with caution and attention to detail.

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Section: Introductionmentioning

confidence: 99%

Transgene‐mediated skeletal phenotypic variation in zebrafish

Kimmel

Wind

Oliva

et al. 2020

Journal of Fish Biology

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“…Studying early life-stage gene expression jointly with morphology can thus provide insight into developmental processes initiating phenotypic variation (e.g. [ 32 ]). Gene expression patterns have been linked to phenotypic divergence between different morphs in several taxa [ 31 – 36 ], but early life-stage variation in gene expression and morphology within morphs have been less well-studied.…”

Section: Introductionmentioning

confidence: 99%

“…We study variation among seven families, with family effects reflecting a combination of direct genetic and non-genetic parental effects. We studied eight growth-related genes (chosen from the literature based on their involvement during early development, [ 29 ]) and six genes related to skeletogenesis (based on findings in a previous study, [ 32 ]). Combining this previously collected gene expression data [ 29 ] with data on offspring morphology, we test the following predictions: 1) if there are genetic and/or parental effects in shape at early life-stages, we should see differences among families in craniofacial features; 2) if early life-stage phenotypic variation is related to genes involved in growth and skeletogenesis of trophic structures, offspring craniofacial shape should covary with the expression of the chosen candidate genes, and 3) if maternal investment (i.e.…”

Section: Introductionmentioning

confidence: 99%

Differences among families in craniofacial shape at early life-stages of Arctic charr (Salvelinus alpinus)

et al. 2020

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Background Organismal fitness can be determined at early life-stages, but phenotypic variation at early life-stages is rarely considered in studies on evolutionary diversification. The trophic apparatus has been shown to contribute to sympatric resource-mediated divergence in several taxa. However, processes underlying diversification in trophic traits are poorly understood. Using phenotypically variable Icelandic Arctic charr (Salvelinus alpinus), we reared offspring from multiple families under standardized laboratory conditions and tested to what extent family (i.e. direct genetic and maternal effects) contributes to offspring morphology at hatching (H) and first feeding (FF). To understand the underlying mechanisms behind early life-stage variation in morphology, we examined how craniofacial shape varied according to family, offspring size, egg size and candidate gene expression. Results Craniofacial shape (i.e. the Meckel’s cartilage and hyoid arch) was more variable between families than within families both across and within developmental stages. Differences in craniofacial morphology between developmental stages correlated with offspring size, whilst within developmental stages only shape at FF correlated with offspring size, as well as female mean egg size. Larger offspring and offspring from females with larger eggs consistently had a wider hyoid arch and contracted Meckel’s cartilage in comparison to smaller offspring. Conclusions This study provides evidence for family-level variation in early life-stage trophic morphology, indicating the potential for parental effects to facilitate resource polymorphism.

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“…Studying early life-stage gene expression jointly with morphology can thus provide insight into developmental processes initiating phenotypic variation (e.g. 32). Gene expression patterns have been linked to phenotypic divergence between different morphs in several taxa (31,(31)(32)(33)(34)(35)(36), but early life-stage variation in gene expression and morphology within morphs have been less well-studied.…”

Section: Introductionmentioning

confidence: 99%

“…32). Gene expression patterns have been linked to phenotypic divergence between different morphs in several taxa (31,(31)(32)(33)(34)(35)(36), but early life-stage variation in gene expression and morphology within morphs have been less well-studied. Particularly at early life-stages, variation in gene expression and morphology can be in uenced by parental effects, for instance as differential distribution of maternal resources (i.e.…”

Section: Introductionmentioning

confidence: 99%

Differences among families in craniofacial shape at early life-stages of Arctic charr (Salvelinus alpinus)

Beck

Räsänen

LeBlanc

et al. 2020

Preprint

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Background Organismal fitness can be determined at early life-stages, but phenotypic variation at early life-stages is rarely considered in studies on evolutionary diversification. The trophic apparatus has been shown to contribute to sympatric resource-mediated divergence in several taxa. However, processes underlying diversification in trophic traits are poorly understood. Using phenotypically variable Icelandic Arctic charr (Salvelinus alpinus), we reared offspring from multiple families under standardized laboratory conditions and tested to what extent family (i.e. direct genetic and maternal effects) contributes to offspring morphology at hatching (H) and first feeding (FF). To understand the underlying mechanisms behind early life-stage variation in morphology, we examined how craniofacial shape varied according to family, offspring size, egg size and candidate gene expression. Results Craniofacial shape (i.e. the Meckel’s cartilage and hyoid arch) was more variable between families than within families both across and within developmental stages. Differences in craniofacial morphology between developmental stages correlated with offspring size, whilst within developmental stages only shape at FF correlated with offspring size, as well as female mean egg size. Larger offspring and offspring from females with larger eggs consistently had a wider hyoid arch and contracted Meckel’s cartilage in comparison to smaller offspring.Conclusions This study provides evidence for family-level variation in early life-stage trophic morphology, indicating the potential for parental effects to facilitate resource polymorphism.

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Selective breeding modifies mef2ca mutant incomplete penetrance by tuning the opposing Notch pathway

Cited by 15 publications

References 69 publications

Transgene‐mediated skeletal phenotypic variation in zebrafish

Transgene‐mediated skeletal phenotypic variation in zebrafish

Differences among families in craniofacial shape at early life-stages of Arctic charr (Salvelinus alpinus)

Differences among families in craniofacial shape at early life-stages of Arctic charr (Salvelinus alpinus)

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