Thyroid specification: The heart-touching stories of FGF and BMP
| Autor: | Haerlingen, Benoit |
|---|---|
| Přispěvatelé: | Costagliola, Sabine, Langer, Ingrid, Migeotte, Isabelle, Boom, Alain, Louryan, Stéphane, Pierreux, Christophe, Fagman, Henrik |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Popis: | Thyroid development is a complex morphogenetic process that is still poorly character- ised. A recurrent theme in endoderm-derived organ development is the tissue-tissue inter- actions between the developing organ and the adjacent mesoderm. In the case of thyroid, the cardiac mesoderm has been proposed to interact with the forming thyroid to guide its development. However, little was known regarding the signals that mediate these interac- tions and how the foregut endoderm integrates them to develop thyroid tissue. In this work, I exploited zebrafish embryos as a platform to perform a small molecule screen to identify the morphogen signalling pathways involved in thyroid specification. This screen revealed that BMP and FGF are the most critical pathways for thyroid development as their inhibition blocks thyroid specification. Next, I mapped the activity profile of BMP and FGF in the pharyngeal area using biosensor lines. It appeared that BMP and FGF are highly active in thyroid progenitors during specification. Of note, the highest BMP and FGF activities were observed near the heart, arguing that cardiac mesoderm secretes the BMP and FGF ligands required for thyroid specification. Also, BMP or FGF modulation effects on the thyroid is stage-dependent; BMP inhibition during mid-somitogenesis does not affect thyroid speci- fication, while early and late-somitogenesis inhibition prevents it. FGF seems to act only once, during late somitogenesis. Moreover, we observed that BMP modulations affect the same way the FGF pathway — on the short and long terms: brief BMP inhibition during early somitogenesis reduces endodermal FGF activity at the thyroid specification stage. Then, preliminary heart ablation experiments showed a direct correlation between the number of differentiated cardiomyocytes and of thyroid progenitors, thus suggesting that the cardiac mesoderm provides the thyroid specification-inducing signals. Altogether, these data sup- port a model in which cardiac mesoderm drives thyroid specification by secreting BMP or FGF ligands. The related BMP and FGF signalling pathways would act in reiterative and co- ordinated manners to promote thyroid specification. Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) info:eu-repo/semantics/nonPublished |
| Databáze: | OpenAIRE |
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