Zebrafish cdx1b regulates expression of downstream factors of Nodal signaling during early endoderm formation

Pei Yi Cheng, Chia Chi Lin, Chun Shiu Wu, Yu Fen Lu, Che Yi Lin, Chih Ching Chung, Cheng Ying Chu, Chang Jen Huang, Chun Yen Tsai, Svetlana Korzh, Jen Leih Wu, Sheng Ping L Hwang

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We identified a zebrafish caudal-related homeobox (cdx1b) gene, which shares syntenic conservation with both human and mouse Cdx1. Zebrafish cdx1b transcripts are maternally deposited. cdx1b is uniformly expressed in both epiblast and hypoblast cells from late gastrulation to the 1-2s stages and can be identified in the retinas, brain and somites during 18-22 hpf stages. After 28 hours of development, cdx1b is exclusively expressed in the developing intestine. Both antisense morpholino oligonucleotide-mediated knockdown and overexpression experiments were conducted to analyze cdx1b function. Hypoplastic development of the liver and pancreas and intestinal abnormalities were observed in 96 hpf cdx1b morphants. In 85% epiboly cdx1b morphants, twofold decreases in the respective numbers of gata5-, cas-, foxa2- and sox17-expressing endodermal precursors were identified. Furthermore, ectopic cdx1b expression caused substantial increases in the respective numbers of gata5-, cas-, foxa2- and sox17-expressing endodermal precursors and altered their distribution patterns in 85% epiboly injected embryos. Conserved Cdx1-binding motifs were identified in both gata5 and foxa2 genes by interspecific sequence comparisons. Cdx1b can bind to the Cdx1-binding motif located in intron 1 of the foxa2 gene based on an electrophoretic mobility shift assay. Co-injection of either zebrafish or mouse foxa2 mRNA with the cdx1b MO rescued the expression domains of ceruloplasmin in the liver of 53 hpf injected embryos. These results indicate that zebrafish cdx1b regulates foxa2 expression and may also modulate gata5 expression, thus affecting early endoderm formation. This study underscores a novel role of zebrafish cdx1b in the development of different digestive organs compared with its mammalian homologs.

Original languageEnglish
Pages (from-to)941-952
Number of pages12
JournalDevelopment
Volume135
Issue number5
DOIs
Publication statusPublished - Mar 2008
Externally publishedYes

Fingerprint

Endoderm
Zebrafish
Germ Layers
Embryonic Structures
Synteny
Morpholinos
Somites
Gastrulation
Ceruloplasmin
Antisense Oligonucleotides
Homeobox Genes
Liver
Electrophoretic Mobility Shift Assay
Introns
Genes
Intestines
Retina
Pancreas
Messenger RNA
Injections

Keywords

  • cdx1b
  • Digestive organ development
  • Nodal signaling
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Cheng, P. Y., Lin, C. C., Wu, C. S., Lu, Y. F., Lin, C. Y., Chung, C. C., ... Hwang, S. P. L. (2008). Zebrafish cdx1b regulates expression of downstream factors of Nodal signaling during early endoderm formation. Development, 135(5), 941-952. https://doi.org/10.1242/dev.010595

Zebrafish cdx1b regulates expression of downstream factors of Nodal signaling during early endoderm formation. / Cheng, Pei Yi; Lin, Chia Chi; Wu, Chun Shiu; Lu, Yu Fen; Lin, Che Yi; Chung, Chih Ching; Chu, Cheng Ying; Huang, Chang Jen; Tsai, Chun Yen; Korzh, Svetlana; Wu, Jen Leih; Hwang, Sheng Ping L.

In: Development, Vol. 135, No. 5, 03.2008, p. 941-952.

Research output: Contribution to journalArticle

Cheng, PY, Lin, CC, Wu, CS, Lu, YF, Lin, CY, Chung, CC, Chu, CY, Huang, CJ, Tsai, CY, Korzh, S, Wu, JL & Hwang, SPL 2008, 'Zebrafish cdx1b regulates expression of downstream factors of Nodal signaling during early endoderm formation', Development, vol. 135, no. 5, pp. 941-952. https://doi.org/10.1242/dev.010595
Cheng, Pei Yi ; Lin, Chia Chi ; Wu, Chun Shiu ; Lu, Yu Fen ; Lin, Che Yi ; Chung, Chih Ching ; Chu, Cheng Ying ; Huang, Chang Jen ; Tsai, Chun Yen ; Korzh, Svetlana ; Wu, Jen Leih ; Hwang, Sheng Ping L. / Zebrafish cdx1b regulates expression of downstream factors of Nodal signaling during early endoderm formation. In: Development. 2008 ; Vol. 135, No. 5. pp. 941-952.
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abstract = "We identified a zebrafish caudal-related homeobox (cdx1b) gene, which shares syntenic conservation with both human and mouse Cdx1. Zebrafish cdx1b transcripts are maternally deposited. cdx1b is uniformly expressed in both epiblast and hypoblast cells from late gastrulation to the 1-2s stages and can be identified in the retinas, brain and somites during 18-22 hpf stages. After 28 hours of development, cdx1b is exclusively expressed in the developing intestine. Both antisense morpholino oligonucleotide-mediated knockdown and overexpression experiments were conducted to analyze cdx1b function. Hypoplastic development of the liver and pancreas and intestinal abnormalities were observed in 96 hpf cdx1b morphants. In 85{\%} epiboly cdx1b morphants, twofold decreases in the respective numbers of gata5-, cas-, foxa2- and sox17-expressing endodermal precursors were identified. Furthermore, ectopic cdx1b expression caused substantial increases in the respective numbers of gata5-, cas-, foxa2- and sox17-expressing endodermal precursors and altered their distribution patterns in 85{\%} epiboly injected embryos. Conserved Cdx1-binding motifs were identified in both gata5 and foxa2 genes by interspecific sequence comparisons. Cdx1b can bind to the Cdx1-binding motif located in intron 1 of the foxa2 gene based on an electrophoretic mobility shift assay. Co-injection of either zebrafish or mouse foxa2 mRNA with the cdx1b MO rescued the expression domains of ceruloplasmin in the liver of 53 hpf injected embryos. These results indicate that zebrafish cdx1b regulates foxa2 expression and may also modulate gata5 expression, thus affecting early endoderm formation. This study underscores a novel role of zebrafish cdx1b in the development of different digestive organs compared with its mammalian homologs.",
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