ABSTRACT: Development of the embryonic head: Modelling the impact of WNT signalling activity on the differentiation of epiblast cells to neural progenitors [Dkk]
Project description:The impact of WNT signalling activity on the acquisition and restriction of lineage propensity of germ layer progenitors and the gene network activity for cell fate decision during the development of the embryonic head was modelled in the epiblast stem cells derived and maintained under different signalling conditions. Our findings showed that the modulation of WNT activity is critical for the specification of the anterior (head) tissue progenitors in the multipotent early epiblast and the repression of WNT activity enhances the ectoderm lineage potency of the epiblast cells and poises the activation of endogenous WNT activity that drives neurogenesis during head morphogenesis.
Project description:The modulation of WNT activity is critical for the specification of the anterior (head) tissue progenitors in the multipotent early epiblast and the repression of WNT activity enhances the ectoderm lineage potency of the epiblast cells and poises the activation of endogenous WNT activity that drives neurogenesis during head morphogenesis.
Project description:To define the sequence of events that lead to the generation of somatic motor neurons (MNs), we took advantage of ESCs, which can be directed to differentiate into spinal neural progenitors (NPs) in vitro (Gouti et al. 2014). This method relies on the exposure of ESCs, cultured as a monolayer, to a brief pulse of Wnt signalling prior to neural induction. Subsequently, removal of Wnt signalling and exposure to retinoic acid (RA) results in the generation of NPs. Exposure of these NPs to Shh signalling agonist SAG induces the expression of genes expressed in the ventral spinal cord and the induction of MNs.
Project description:The development of the embryonic head in mice relies on the activity of the transcription factor LIM homeobox 1 (LHX1) in the anterior epiblast. In this study, we sought to unravel the molecular role of LHX1 during and immediately following gastrulation. We utilized CRISPR-Cas9 gene editing in embryo models as well as DamID-seq, RNA-seq, and ATAC-seq in mouse embryos. These techniques enabled us to reveal the genome wide targets of LHX1 for the first time in gastrulation stage mouse embryos. Integrated analysis of the omics datasets uncovered that LHX1 is instrumental in decommissioning the pluripotency network and determining the anterior fate of the precursor tissue of the embryonic head. We found that LHX1 directly binds to and regulates genes involved in WNT and FGF signaling pathway inhibition. We also identified a downstream target of LHX1, Kctd1, expressed in the anterior tissue, which acts to modulate canonical WNT activity. These findings identified a component of the gene regulatory network anchored by LHX1 that governs the development of the embryonic head.
Project description:The development of the embryonic head in mice relies on the activity of the transcription factor LIM homeobox 1 (LHX1) in the anterior epiblast. In this study, we sought to unravel the molecular role of LHX1 during and immediately following gastrulation. We utilized CRISPR-Cas9 gene editing in embryo models as well as DamID-seq, RNA-seq, and ATAC-seq in mouse embryos. These techniques enabled us to reveal the genome wide targets of LHX1 for the first time in gastrulation stage mouse embryos. Integrated analysis of the omics datasets uncovered that LHX1 is instrumental in decommissioning the pluripotency network and determining the anterior fate of the precursor tissue of the embryonic head. We found that LHX1 directly binds to and regulates genes involved in WNT and FGF signaling pathway inhibition. We also identified a downstream target of LHX1, Kctd1, expressed in the anterior tissue, which acts to modulate canonical WNT activity. These findings identified a component of the gene regulatory network anchored by LHX1 that governs the development of the embryonic head.
Project description:The development of the embryonic head in mice relies on the activity of the transcription factor LIM homeobox 1 (LHX1) in the anterior epiblast. In this study, we sought to unravel the molecular role of LHX1 during and immediately following gastrulation. We utilized CRISPR-Cas9 gene editing in embryo models as well as DamID-seq, RNA-seq, and ATAC-seq in mouse embryos. These techniques enabled us to reveal the genome wide targets of LHX1 for the first time in gastrulation stage mouse embryos. Integrated analysis of the omics datasets uncovered that LHX1 is instrumental in decommissioning the pluripotency network and determining the anterior fate of the precursor tissue of the embryonic head. We found that LHX1 directly binds to and regulates genes involved in WNT and FGF signaling pathway inhibition. We also identified a downstream target of LHX1, Kctd1, expressed in the anterior tissue, which acts to modulate canonical WNT activity. These findings identified a component of the gene regulatory network anchored by LHX1 that governs the development of the embryonic head.
Project description:The development of the embryonic head in mice relies on the activity of the transcription factor LIM homeobox 1 (LHX1) in the anterior epiblast. In this study, we sought to unravel the molecular role of LHX1 during and immediately following gastrulation. We utilized CRISPR-Cas9 gene editing in embryo models as well as DamID-seq, RNA-seq, and ATAC-seq in mouse embryos. These techniques enabled us to reveal the genome wide targets of LHX1 for the first time in gastrulation stage mouse embryos. Integrated analysis of the omics datasets uncovered that LHX1 is instrumental in decommissioning the pluripotency network and determining the anterior fate of the precursor tissue of the embryonic head. We found that LHX1 directly binds to and regulates genes involved in WNT and FGF signaling pathway inhibition. We also identified a downstream target of LHX1, Kctd1, expressed in the anterior tissue, which acts to modulate canonical WNT activity. These findings identified a component of the gene regulatory network anchored by LHX1 that governs the development of the embryonic head.
Project description:The development of the embryonic head in mice relies on the activity of the transcription factor LIM homeobox 1 (LHX1) in the anterior epiblast. In this study, we sought to unravel the molecular role of LHX1 during and immediately following gastrulation. We utilized CRISPR-Cas9 gene editing in embryo models as well as DamID-seq, RNA-seq, and ATAC-seq in mouse embryos. These techniques enabled us to reveal the genome wide targets of LHX1 for the first time in gastrulation stage mouse embryos. Integrated analysis of the omics datasets uncovered that LHX1 is instrumental in decommissioning the pluripotency network and determining the anterior fate of the precursor tissue of the embryonic head. We found that LHX1 directly binds to and regulates genes involved in WNT and FGF signaling pathway inhibition. We also identified a downstream target of LHX1, Kctd1, expressed in the anterior tissue, which acts to modulate canonical WNT activity. These findings identified a component of the gene regulatory network anchored by LHX1 that governs the development of the embryonic head.
