Project description:The endostyle is an endodermal organ unique to non-vertebrate chordates except for lamprey larvae, where it serves as forerunner to the adult thyroid. Here, we examine if the acquisition of neural crest in the vertebrate lineage played a role in the elaboration of the endostyle. CM-DiI lineage tracing reveals a neural crest contribution to the endostyle, and CRISPR/Cas9 mutagenesis of key neural crest genes causes endostyle defects including formation of a single rather than bilobed structure. RNA-sequencing reveals gene profiles characteristic of embryonic neural crest cells and Schwann cell precursors in the developing endostyle. Contrasting with the prevailing view that the endostyle is an endoderm-derived organ, we propose that the acquisition of the neural crest played a critical step in promoting thyroid evolution from chordate endostyle.
Project description:We present a comprehensive proteome atlas of the model chordate Ciona, covering eight developmental stages and ~7k translated genes as well as a deep quantitative atlas of maternal proteins found in the Ciona egg.
Project description:Thyroid nodules occur in about 60% of the population. Current diagnostic strategies, however, often fail at distinguishing malignant nodules before surgery, thus leading to unnecessary, invasive treatments. As proteins are involved in all physio/pathological processes, a proteome investigation of biopsied nodules may help correctly classify and identify malignant nodules and discover therapeutic targets. Quantitative mass spectrometry data-independent acquisition (DIA) enables highly reproducible and rapid throughput investigation of proteomes. An exhaustive spectral library of thyroid nodules is essential for DIA yet still unavailable. This study presents a comprehensive thyroid spectral library covering five types of thyroid tissue: multinodular goiter, follicular adenoma, follicular and papillary thyroid carcinoma, and normal thyroid tissue. Our library includes 925,330 transition groups, 157,548 peptide precursors, 121,960 peptides, 9941 protein groups, and 9826 proteins from proteotypic peptides. This library resource was evaluated using three papillary thyroid carcinoma samples and their corresponding adjacent normal thyroid tissue, leading to effective quantification of up to 7863 proteins from biopsy-level thyroid tissues.
Project description:Acquisition of dorsal structures, such as notochord and hollow nerve cord, is likely to have had a profound influence upon vertebrate evolution. Dorsal formation in chordate development thus has been intensively studied in vertebrates and ascidians. However, the present understanding does not explain how chordates acquired dorsal structures. Here we show that amphioxus retains a key clue to answer this question. In amphioxus embryos, maternal nodal mRNA distributes asymmetrically in accordance with the remodelling of the cortical cytoskeleton in the fertilized egg, and subsequently lefty is first expressed in a patch of blastomeres across the equator where wnt8 is expressed circularly and which will become the margin of the blastopore. The lefty domain co-expresses zygotic nodal by the initial gastrula stage on the one side of the blastopore margin and induces the expression of goosecoid, not-like, chordin and brachyury1 genes in this region, as in the oral ectoderm of sea urchin embryos, which provides a basis for the formation of the dorsal structures. The striking similarity in the gene regulations and their respective expression domains when comparing dorsal formation in amphioxus and the determination of the oral ectoderm in sea urchin embryos suggests that chordates derived from an ambulacrarian-type blastula with dorsoventral inversion.
Project description:Human neural crest cell development progresses via a pre-neural border (pNB) cell state that precedes the induction of the neurectoderm and the neural border. Here, we identify a set of pNB gene candidates, including forkhead box B1 (FOXB1), and their associated enhancers, that are rapidly activated by β-catenin-mediated signaling during human embryonic stem (ES) cell differentiation towards neural crest cells. FOXB1 simultaneously maintains neuroectoderm competency and controls the timing of differentiating ES cells to acquire neural crest fate by directly targeting key neural crest and neural progenitor loci in a context-dependent manner. Notably, the transient expression of FOXB1 in pre-neural crest cells also establishes autonomic neurogenic potential in mature neural crest cells, likely via its regulation of the expression of ASCL1, a master regulator of autonomic neurons. Altogether, our data implicates pNB cell state as the missing link bridging the exit of pluripotency to the acquisition of neural crest fate and its diverse ecto-mesenchymal differentiation potentials.
Project description:We utilized quantitative analyses of the proteome, transcriptome, and ubiquitinome to study how ubiquitination and NEDD4 control neural crest cell survival and stem-cell-like properties. We report 276 novel NEDD4 targets in neural crest cells and show that loss of NEDD4 leads to a striking global reduction in specific ubiquitin lysine linkages.