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B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo.

Okuda Y, Ogura E, Kondoh H, Kamachi Y - PLoS Genet. (2010)

Bottom Line: Chromatin immunoprecipitation analysis of the her3, hesx1, neurog1, pcdh18a, and cyp26a1 genes further suggests a direct regulation of these genes by B1 SOX.We also found an interesting overlap between the early phenotypes of the B1 sox quadruple knockdown embryos and the maternal-zygotic spg embryos that are devoid of pou5f1 activity.These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 sox functions are central to coordinating cell fate specification with patterning and morphogenetic processes occurring in the early embryo.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.

ABSTRACT
The B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through in situ hybridization, RT-PCR, and microarray analyses. Importantly, these phenotypic analyses revealed that the B1 SOX proteins regulate the following distinct processes: (1) early dorsoventral patterning by controlling bmp2b/7; (2) gastrulation movements via the regulation of pcdh18a/18b and wnt11, a non-canonical Wnt ligand gene; (3) neural differentiation by regulating the Hes-class bHLH gene her3 and the proneural-class bHLH genes neurog1 (positively) and ascl1a (negatively), and regional transcription factor genes, e.g., hesx1, zic1, and rx3; and (4) neural patterning by regulating signaling pathway genes, cyp26a1 in RA signaling, oep in Nodal signaling, shh, and mdkb. Chromatin immunoprecipitation analysis of the her3, hesx1, neurog1, pcdh18a, and cyp26a1 genes further suggests a direct regulation of these genes by B1 SOX. We also found an interesting overlap between the early phenotypes of the B1 sox quadruple knockdown embryos and the maternal-zygotic spg embryos that are devoid of pou5f1 activity. These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 sox functions are central to coordinating cell fate specification with patterning and morphogenetic processes occurring in the early embryo.

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Summary of embryonic stage-dependent target gene regulation by B1 SOX.The B1 sox expression domains are schematically illustrated at the top. The B1 SOX-downstream genes that were identified in this study are shown with possible time windows for regulation. The major downstream genes of B1 SOX were found to be developmental transcription factor genes (indicated in blue), signaling pathway genes (red) and cell adhesion molecule genes (green). Our data indicate that, in these regulations, B1 SOX primarily act as activators and appear to indirectly repress several target genes through the activation of hypothetical repressors. A direct regulation of the pcdh18a, her3, hesx1, cyp26a1 and neurog1 genes by B1 SOX is suggested by our ChIP analysis (indicated by blue arrows). The developmental effects of the regulation by B1 SOX are indicated on the right.
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pgen-1000936-g008: Summary of embryonic stage-dependent target gene regulation by B1 SOX.The B1 sox expression domains are schematically illustrated at the top. The B1 SOX-downstream genes that were identified in this study are shown with possible time windows for regulation. The major downstream genes of B1 SOX were found to be developmental transcription factor genes (indicated in blue), signaling pathway genes (red) and cell adhesion molecule genes (green). Our data indicate that, in these regulations, B1 SOX primarily act as activators and appear to indirectly repress several target genes through the activation of hypothetical repressors. A direct regulation of the pcdh18a, her3, hesx1, cyp26a1 and neurog1 genes by B1 SOX is suggested by our ChIP analysis (indicated by blue arrows). The developmental effects of the regulation by B1 SOX are indicated on the right.

Mentions: Previous studies have suggested that the group B1 sox genes are critical for early processes in embryogenesis, particularly during early neural development [1]–[6]. Possibly as a consequence of functional redundancy, however, loss-of-function analyses have not been sufficiently informative to date. In our present study, we successfully depleted the B1 sox activity from early zebrafish embryos by a quadruple knockdown of sox2/3/19a/19b, and present clear evidence that the B1 sox genes are highly redundant and their encoding proteins are functionally interchangeable in early zebrafish embryogenesis. More importantly, we demonstrate that the B1 sox genes are indeed essential for several key processes during early embryogenesis, namely embryonic patterning, gastrulation movements and neural development. The major downstream genes of B1 SOX that function in these processes were found to be developmental transcription factor genes, signaling pathway genes and cell adhesion molecule genes (Figure 8). These data indicate that B1 SOX proteins play a central role in coordinating cell fate specification with embryo patterning and morphogenetic processes by controlling a wide variety of developmental regulators in a process-dependent manner. Among the broad functions of B1 SOX, the transcriptional partnership with Pou5f1 is critical for early embryogenesis from the blastoderm to early neural stages as detailed further below.


B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo.

Okuda Y, Ogura E, Kondoh H, Kamachi Y - PLoS Genet. (2010)

Summary of embryonic stage-dependent target gene regulation by B1 SOX.The B1 sox expression domains are schematically illustrated at the top. The B1 SOX-downstream genes that were identified in this study are shown with possible time windows for regulation. The major downstream genes of B1 SOX were found to be developmental transcription factor genes (indicated in blue), signaling pathway genes (red) and cell adhesion molecule genes (green). Our data indicate that, in these regulations, B1 SOX primarily act as activators and appear to indirectly repress several target genes through the activation of hypothetical repressors. A direct regulation of the pcdh18a, her3, hesx1, cyp26a1 and neurog1 genes by B1 SOX is suggested by our ChIP analysis (indicated by blue arrows). The developmental effects of the regulation by B1 SOX are indicated on the right.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865518&req=5

pgen-1000936-g008: Summary of embryonic stage-dependent target gene regulation by B1 SOX.The B1 sox expression domains are schematically illustrated at the top. The B1 SOX-downstream genes that were identified in this study are shown with possible time windows for regulation. The major downstream genes of B1 SOX were found to be developmental transcription factor genes (indicated in blue), signaling pathway genes (red) and cell adhesion molecule genes (green). Our data indicate that, in these regulations, B1 SOX primarily act as activators and appear to indirectly repress several target genes through the activation of hypothetical repressors. A direct regulation of the pcdh18a, her3, hesx1, cyp26a1 and neurog1 genes by B1 SOX is suggested by our ChIP analysis (indicated by blue arrows). The developmental effects of the regulation by B1 SOX are indicated on the right.
Mentions: Previous studies have suggested that the group B1 sox genes are critical for early processes in embryogenesis, particularly during early neural development [1]–[6]. Possibly as a consequence of functional redundancy, however, loss-of-function analyses have not been sufficiently informative to date. In our present study, we successfully depleted the B1 sox activity from early zebrafish embryos by a quadruple knockdown of sox2/3/19a/19b, and present clear evidence that the B1 sox genes are highly redundant and their encoding proteins are functionally interchangeable in early zebrafish embryogenesis. More importantly, we demonstrate that the B1 sox genes are indeed essential for several key processes during early embryogenesis, namely embryonic patterning, gastrulation movements and neural development. The major downstream genes of B1 SOX that function in these processes were found to be developmental transcription factor genes, signaling pathway genes and cell adhesion molecule genes (Figure 8). These data indicate that B1 SOX proteins play a central role in coordinating cell fate specification with embryo patterning and morphogenetic processes by controlling a wide variety of developmental regulators in a process-dependent manner. Among the broad functions of B1 SOX, the transcriptional partnership with Pou5f1 is critical for early embryogenesis from the blastoderm to early neural stages as detailed further below.

Bottom Line: Chromatin immunoprecipitation analysis of the her3, hesx1, neurog1, pcdh18a, and cyp26a1 genes further suggests a direct regulation of these genes by B1 SOX.We also found an interesting overlap between the early phenotypes of the B1 sox quadruple knockdown embryos and the maternal-zygotic spg embryos that are devoid of pou5f1 activity.These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 sox functions are central to coordinating cell fate specification with patterning and morphogenetic processes occurring in the early embryo.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.

ABSTRACT
The B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through in situ hybridization, RT-PCR, and microarray analyses. Importantly, these phenotypic analyses revealed that the B1 SOX proteins regulate the following distinct processes: (1) early dorsoventral patterning by controlling bmp2b/7; (2) gastrulation movements via the regulation of pcdh18a/18b and wnt11, a non-canonical Wnt ligand gene; (3) neural differentiation by regulating the Hes-class bHLH gene her3 and the proneural-class bHLH genes neurog1 (positively) and ascl1a (negatively), and regional transcription factor genes, e.g., hesx1, zic1, and rx3; and (4) neural patterning by regulating signaling pathway genes, cyp26a1 in RA signaling, oep in Nodal signaling, shh, and mdkb. Chromatin immunoprecipitation analysis of the her3, hesx1, neurog1, pcdh18a, and cyp26a1 genes further suggests a direct regulation of these genes by B1 SOX. We also found an interesting overlap between the early phenotypes of the B1 sox quadruple knockdown embryos and the maternal-zygotic spg embryos that are devoid of pou5f1 activity. These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 sox functions are central to coordinating cell fate specification with patterning and morphogenetic processes occurring in the early embryo.

Show MeSH
Related in: MedlinePlus