An update of key morphogenetic events of thyroid development in Zebrafish

Physiology 2021 (2021) Proc Physiol Soc 48, SA29

Research Symposium: An update of key morphogenetic events of thyroid development in Zebrafish

Federica Marelli1, Luca Persani1, 2

1 IRCCS Istituto Auxologico Italiano, Milano, Italy 2 Università degli Studi di Milano, Milano, Italy

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The thyroid gland is a highly conserved organ in vertebrates that regulates a wide range of developmental processes and controls the homeostasis of fundamental physiological mechanisms.  Defects during thyroid development can lead to irreversible intellectual disabilities and dwarfism if not timely diagnosed and treated. Therefore, the mechanisms underlying thyroid gland development have a central interest in biology, and zebrafish represents a valuable model to study thyroid physiology with significant advantages compared to the mammalian models (1. Zebrafish is an emerging powerful vertebrate model for thyroid research due to its external fertilization, transparency of developing embryos and rapid organ development. Moreover, the availability of molecular tools for the manipulation of zebrafish genome allows the generation of targeted-genetic mutants or transgenic lines that express fluorescent proteins into specific cell types. Thanks to this, we are now able to study the relative contribution of different genes during thyroid development, and track the dynamic changes in thyroid shape, size, and location in live embryos (2). During zebrafish embryogenesis, the acquisition of thyroid competence occurs between the 20-24 hours post fertilization (hpf), when a restricted group of pharyngeal endoderm cells start to express the thyroid transcription factors (TTFs) pax2a, nkx2.4b and hhex, forming the so-called thyroid anlage. Around 36-40 hpf, the thyroid anlage expands forming a placode that protrudes into the underlying mesenchyme and buds from the pharyngeal epithelium in a rostro-ventral direction, in close proximity to the developing heart tube. The first detectable thyroid follicular cell (TFC) is formed by 55 hpf and expresses all of the functional thyroid markers, such as thyroglobulin (tg), tthyroperoxidase (tpo), Na/I symporter (slc5a5), and thyroid stimulating hormone receptor (tshr) required for thyroid hormone synthesis. During the later stages of thyroid organogenesis (55-72 hpf), the TFCs proliferate and migrate posteriorly forming distinct follicular units scattered along the pharyngeal midline, moving close and along the ventral aorta (2). Among the various organs derived from foregut endoderm, the thyroid gland is unique because a complex crosstalk between intrinsic and extrinsic factors coming from surrounding tissues (e.g., cardiac mesoderm and pharyngeal vessels) is essential for proper thyroid organogenesis. In particular, the coordinate activity of different morphogens (Notch, Shh, Bmp, Fgf, and Wnt) during critical developmental windows of thyroid development have been recently described in zebrafish (3-5). During the symposium, we will present the recent findings produced in the various zebrafish experimental models with the aim to define a comprehensive picture of the morphogenetic events underlying zebrafish thyroid development. 



Where applicable, experiments conform with Society ethical requirements.

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