XB-ART-58588Mol Cells 2021 Oct 31;4410:723-735. doi: 10.14348/molcells.2021.0055.
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Goosecoid Controls Neuroectoderm Specification via Dual Circuits of Direct Repression and Indirect Stimulation in Xenopus Embryos.
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.
PubMed ID: 34711690
Article link: Mol Cells
Species referenced: Xenopus laevis
Genes referenced: acss2.2 ascl1 bmp4 chrd.1 churc1 eef1a1 egr2 fgf8 foxd4l1.1 gsc hoxb9 krt12.4 ncam1 neurod1 neurog2 nog otx2 tbxt ventx1 ventx2.2 zic3
Morpholinos: nog MO3 nog MO4
gRNAs referenced: foxd4l1.1 gRNA1
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References [+] :
Artinger, Interaction of goosecoid and brachyury in Xenopus mesoderm patterning. 1997, Pubmed, Xenbase