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Published on: February 22, 2019
Zebrafish bcl2l is a survival factor in thyroid development
Immacolata Porreca1, Elena De Felice, Henrik Fagman
1IRGS, Biogem, Via Camporeale, 83031 Ariano Irpino, Avellino, Italy.
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.
Insights
The bcl2-like (bcl2l) gene is crucial for thyroid cell survival during development, inhibiting apoptosis. This survival mechanism is regulated by specific transcription factors in zebrafish thyroid precursors.
Area of Science:
- Developmental Biology
- Endocrinology
- Cell Death Research
Background:
- Regulated cell death, or apoptosis, is vital for organ development.
- Thyroid gland development mechanisms, particularly cell survival, remain largely unknown.
- Bcl-2 family genes are key regulators of apoptosis.
Purpose of the Study:
- To investigate the role of Bcl-2 family genes in zebrafish thyroid development.
- To understand the cell survival mechanisms during endocrine gland morphogenesis.
- To identify specific genes and transcription factors involved in thyroid precursor cell survival.
Main Methods:
- Utilized the zebrafish model system for studying thyroid development.
- Analyzed gene expression of bcl2-like (bcl2l) in the thyroid primordium.
- Employed morpholino-mediated knockdown and mutant analyses to assess gene function.
- Investigated caspase-3-dependent apoptotic pathways.
Main Results:
- Identified bcl2l gene expression in the zebrafish thyroid primordium.
- Demonstrated that bcl2l is essential for thyroid cell survival.
- Showed that transcription factors pax2a, nk2.1a, and hhex modulate bcl2l function.
- Revealed bcl2l controls a caspase-3-dependent apoptotic mechanism.
Conclusions:
- Thyroid precursor cells require active survival mechanisms for proper development.
- The bcl2l gene inhibits cell death during thyroid morphogenesis.
- Thyroid-specific transcription factors directly regulate bcl2l's role in cell survival.
- This study provides the first evidence of an active survival mechanism in the thyroid primordium.

