title: Zebrafish bcl2l is a survival factor in thyroid development.
abstract: Regulated cell death, defined in morphological terms as apoptosis, is crucial for organ morphogenesis. While differentiation of the thyroid gland has been extensively studied, nothing is yet known about the survival mechanisms involved in the development of this endocrine gland. Using the zebrafish model system, we aim to understand whether genes belonging to the Bcl-2 family that control apoptosis are implicated in regulation of cell survival during thyroid development. Evidence of strong Bcl-2 gene expression in mouse thyroid precursors prompted us to investigate the functions played by its zebrafish homologs during thyroid development. We show that the bcl2-like (bcl2l) gene is expressed in the zebrafish thyroid primordium. Morpholino-mediated knockdown and mutant analyses revealed that bcl2l is crucial for thyroid cell survival and that this function is tightly modulated by the transcription factors pax2a, nk2.1a and hhex. Also, the bcl2l gene appears to control a caspase-3-dependent apoptotic mechanism during thyroid development. Thyroid precursor cells require an actively maintained survival mechanism to properly proceed through development. The bcl2l gene operates in the inhibition of cell death under direct regulation of a thyroid specific set of transcription factors. This is the first demonstration of an active mechanism to ensure survival of the thyroid primordium during morphogenesis.
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031 Ariano Irpino, Avellino, Italy.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Porreca
authors.forename: Elena
authors.initials: E
authors.lastname: De Felice
authors.forename: Henrik
authors.initials: H
authors.lastname: Fagman
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Lauro
authors.forename: Paolo
authors.initials: P
authors.lastname: Sordino
mesh_terms: D000818:Animals; D002470:Cell Survival; D019254:Genes, bcl-2; D009024:Morphogenesis; D013961:Thyroid Gland / Q000196:embryology* / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology*; D051020:bcl-X Protein / Q000502:physiology*
chemical_list: D014157:Transcription Factors; D029961:Zebrafish Proteins; D051020:bcl-X Protein; C494810:bcl2l1 protein, zebrafish