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Expression change in Angiopoietin-1 underlies change in relative brain size in fish.

Chen YC, Harrison PW, Kotrschal A, Kolm N, Mank JE, Panula P - Proc. Biol. Sci. (2015)

Bottom Line: Brain size varies substantially across the animal kingdom and is often associated with cognitive ability; however, the genetic architecture underpinning natural variation in these key traits is virtually unknown.Translation inhibition of Ang-1 resulted in smaller brains in larvae and increased expression of Notch-1, which regulates differentiation of neural stem cells.Taken together, our results suggest that the genetic architecture affecting brain size in our population may be surprisingly simple, and Ang-1 may be a potentially important locus in the evolution of vertebrate brain size and cognitive ability.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Center and Institute of Biomedicine, Anatomy, University of Helsinki, Haartmaninkatu 8, Helsinki 00290, Finland.

ABSTRACT
Brain size varies substantially across the animal kingdom and is often associated with cognitive ability; however, the genetic architecture underpinning natural variation in these key traits is virtually unknown. In order to identify the genetic architecture and loci underlying variation in brain size, we analysed both coding sequence and expression for all the loci expressed in the telencephalon in replicate populations of guppies (Poecilia reticulata) artificially selected for large and small relative brain size. A single gene, Angiopoietin-1 (Ang-1), a regulator of angiogenesis and suspected driver of neural development, was differentially expressed between large- and small-brain populations. Zebra fish (Danio rerio) morphants showed that mild knock down of Ang-1 produces a small-brained phenotype that could be rescued with Ang-1 mRNA. Translation inhibition of Ang-1 resulted in smaller brains in larvae and increased expression of Notch-1, which regulates differentiation of neural stem cells. In situ analysis of newborn large- and small-brained guppies revealed matching expression patterns of Ang-1 and Notch-1 to those observed in zebrafish larvae. Taken together, our results suggest that the genetic architecture affecting brain size in our population may be surprisingly simple, and Ang-1 may be a potentially important locus in the evolution of vertebrate brain size and cognitive ability.

No MeSH data available.


Expression profiles of guppy populations. (a) Hierarchical clustering of gene expression across all significantly expressed genes in LBf, LBm, SBf, SBm and PSm, and PSf telencephalons. Clustering is based on Euclidian distance of expression level, with significance provided by 1000 bootstrap replicates shown on each node. Yellow indicates relative higher and black relative lower expression for each transcript. (b) Relative expression of Ang-1 in pre-selected and selected male populations. (c) Relative expression of Ang-1 in pre-selected and selected female populations. In both (b,c), expression is based on log2 relative trimmed mean of M-values (TMM) normalized FPKM mapped reads. Tails indicate minimum and maximum expression values for each population. Significance of expression difference between large- and small-brained population pools, assessed with a t-test, is indicated in each panel (****Padj < 0.0001).
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RSPB20150872F1: Expression profiles of guppy populations. (a) Hierarchical clustering of gene expression across all significantly expressed genes in LBf, LBm, SBf, SBm and PSm, and PSf telencephalons. Clustering is based on Euclidian distance of expression level, with significance provided by 1000 bootstrap replicates shown on each node. Yellow indicates relative higher and black relative lower expression for each transcript. (b) Relative expression of Ang-1 in pre-selected and selected male populations. (c) Relative expression of Ang-1 in pre-selected and selected female populations. In both (b,c), expression is based on log2 relative trimmed mean of M-values (TMM) normalized FPKM mapped reads. Tails indicate minimum and maximum expression values for each population. Significance of expression difference between large- and small-brained population pools, assessed with a t-test, is indicated in each panel (****Padj < 0.0001).

Mentions: Within the selected populations, overall transcriptional similarity was stronger for sex than brain size. Hierarchical clustering [23] indicates that the selected populations are more similar to each other in overall expression than they are to the pre-selected population (figure 1a). This was further supported by the approximately unbiased p-value separating selected from pre-selected populations (based on bootstrapping of expression data, p < 0.05). Furthermore, 13 075 transcripts, corresponding to 8639 genes in Xiphophorus, showed significant differences in expression between pre-selected and selected populations, regardless of brain size (log2-fold change more than 2, Padj < 0.05). Environmental complexity has been shown to affect broad patterns of neural gene expression [40], and the differences we observe in overall transcription between the selected and pre-selected populations are likely an effect of holding conditions, with the pre-selected populations kept within large 100 l aquaria at relatively high density. By contrast, each male–female pair of the selected populations was kept in a 3 l aquarium with occasional offspring removed within hours after birth. The transcriptional differences between the pre-selected and selected populations, although not the focus of this study, illustrate the remarkable effects of social environment and intra-sexual social interactions on overall telencephalon transcription.Figure 1.


Expression change in Angiopoietin-1 underlies change in relative brain size in fish.

Chen YC, Harrison PW, Kotrschal A, Kolm N, Mank JE, Panula P - Proc. Biol. Sci. (2015)

Expression profiles of guppy populations. (a) Hierarchical clustering of gene expression across all significantly expressed genes in LBf, LBm, SBf, SBm and PSm, and PSf telencephalons. Clustering is based on Euclidian distance of expression level, with significance provided by 1000 bootstrap replicates shown on each node. Yellow indicates relative higher and black relative lower expression for each transcript. (b) Relative expression of Ang-1 in pre-selected and selected male populations. (c) Relative expression of Ang-1 in pre-selected and selected female populations. In both (b,c), expression is based on log2 relative trimmed mean of M-values (TMM) normalized FPKM mapped reads. Tails indicate minimum and maximum expression values for each population. Significance of expression difference between large- and small-brained population pools, assessed with a t-test, is indicated in each panel (****Padj < 0.0001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590489&req=5

RSPB20150872F1: Expression profiles of guppy populations. (a) Hierarchical clustering of gene expression across all significantly expressed genes in LBf, LBm, SBf, SBm and PSm, and PSf telencephalons. Clustering is based on Euclidian distance of expression level, with significance provided by 1000 bootstrap replicates shown on each node. Yellow indicates relative higher and black relative lower expression for each transcript. (b) Relative expression of Ang-1 in pre-selected and selected male populations. (c) Relative expression of Ang-1 in pre-selected and selected female populations. In both (b,c), expression is based on log2 relative trimmed mean of M-values (TMM) normalized FPKM mapped reads. Tails indicate minimum and maximum expression values for each population. Significance of expression difference between large- and small-brained population pools, assessed with a t-test, is indicated in each panel (****Padj < 0.0001).
Mentions: Within the selected populations, overall transcriptional similarity was stronger for sex than brain size. Hierarchical clustering [23] indicates that the selected populations are more similar to each other in overall expression than they are to the pre-selected population (figure 1a). This was further supported by the approximately unbiased p-value separating selected from pre-selected populations (based on bootstrapping of expression data, p < 0.05). Furthermore, 13 075 transcripts, corresponding to 8639 genes in Xiphophorus, showed significant differences in expression between pre-selected and selected populations, regardless of brain size (log2-fold change more than 2, Padj < 0.05). Environmental complexity has been shown to affect broad patterns of neural gene expression [40], and the differences we observe in overall transcription between the selected and pre-selected populations are likely an effect of holding conditions, with the pre-selected populations kept within large 100 l aquaria at relatively high density. By contrast, each male–female pair of the selected populations was kept in a 3 l aquarium with occasional offspring removed within hours after birth. The transcriptional differences between the pre-selected and selected populations, although not the focus of this study, illustrate the remarkable effects of social environment and intra-sexual social interactions on overall telencephalon transcription.Figure 1.

Bottom Line: Brain size varies substantially across the animal kingdom and is often associated with cognitive ability; however, the genetic architecture underpinning natural variation in these key traits is virtually unknown.Translation inhibition of Ang-1 resulted in smaller brains in larvae and increased expression of Notch-1, which regulates differentiation of neural stem cells.Taken together, our results suggest that the genetic architecture affecting brain size in our population may be surprisingly simple, and Ang-1 may be a potentially important locus in the evolution of vertebrate brain size and cognitive ability.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Center and Institute of Biomedicine, Anatomy, University of Helsinki, Haartmaninkatu 8, Helsinki 00290, Finland.

ABSTRACT
Brain size varies substantially across the animal kingdom and is often associated with cognitive ability; however, the genetic architecture underpinning natural variation in these key traits is virtually unknown. In order to identify the genetic architecture and loci underlying variation in brain size, we analysed both coding sequence and expression for all the loci expressed in the telencephalon in replicate populations of guppies (Poecilia reticulata) artificially selected for large and small relative brain size. A single gene, Angiopoietin-1 (Ang-1), a regulator of angiogenesis and suspected driver of neural development, was differentially expressed between large- and small-brain populations. Zebra fish (Danio rerio) morphants showed that mild knock down of Ang-1 produces a small-brained phenotype that could be rescued with Ang-1 mRNA. Translation inhibition of Ang-1 resulted in smaller brains in larvae and increased expression of Notch-1, which regulates differentiation of neural stem cells. In situ analysis of newborn large- and small-brained guppies revealed matching expression patterns of Ang-1 and Notch-1 to those observed in zebrafish larvae. Taken together, our results suggest that the genetic architecture affecting brain size in our population may be surprisingly simple, and Ang-1 may be a potentially important locus in the evolution of vertebrate brain size and cognitive ability.

No MeSH data available.