Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Goosecoid Controls Neuroectoderm Specification via Dual Circuits of Direct Repression and Indirect Stimulation in Xenopus Embryos

  • Umair, Zobia (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University) ;
  • Kumar, Vijay (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University) ;
  • Goutam, Ravi Shankar (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University) ;
  • Kumar, Shiv (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University) ;
  • Lee, Unjoo (Department of Electrical Engineering, Hallym University) ;
  • Kim, Jaebong (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University)
  • Received : 2021.03.05
  • Accepted : 2021.08.16
  • Published : 2021.10.31
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Abstract

Spemann organizer is a center of dorsal mesoderm and itself retains the mesoderm character, but it has a stimulatory role for neighboring ectoderm cells in becoming neuroectoderm in gastrula embryos. Goosecoid (Gsc) overexpression in ventral region promotes secondary axis formation including neural tissues, but the role of gsc in neural specification could be indirect. We examined the neural inhibitory and stimulatory roles of gsc in the same cell and neighboring cells contexts. In the animal cap explant system, Gsc overexpression inhibited expression of neural specific genes including foxd4l1.1, zic3, ncam, and neurod. Genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) and promoter analysis of early neural genes of foxd4l1.1 and zic3 were performed to show that the neural inhibitory mode of gsc was direct. Site-directed mutagenesis and serially deleted construct studies of foxd4l1.1 promoter revealed that Gsc directly binds within the foxd4l1.1 promoter to repress its expression. Conjugation assay of animal cap explants was also performed to demonstrate an indirect neural stimulatory role for gsc. The genes for secretory molecules, Chordin and Noggin, were up-regulated in gsc injected cells with the neural fate only achieved in gsc uninjected neighboring cells. These experiments suggested that gsc regulates neuroectoderm formation negatively when expressed in the same cell and positively in neighboring cells via soluble factors. One is a direct suppressive circuit of neural genes in gsc expressing mesoderm cells and the other is an indirect stimulatory circuit for neurogenesis in neighboring ectoderm cells via secreted BMP antagonizers.

Keywords

Acknowledgement

This article was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science, and Technology of Korea (2016R1D1A1B02008770, 2018M3C7A1056285, and 2021M3H9A1097557).

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