![c-cells of thyroid endoderm first aid 2017 c-cells of thyroid endoderm first aid 2017](https://europepmc.org/articles/PMC7048977/bin/atm-08-04-131-f1.jpg)
The so-called thyroid transcription factors – Nkx2-1, Foxe1, Pax8 and Hhex – were the first pieces of the puzzle identified in mice. The use of animal models and pluripotent stem cells has greatly aided in providing clues to the complicated puzzle of thyroid development and function in adults. We will focus on endoderm-derived thyroid epithelial cells, which are responsible for the formation of the thyroid follicle, the functional unit of the thyroid gland. We also discuss the maintenance of the adult differentiated phenotype to ensure the biosynthesis of thyroid hormones. In this Review, we describe the most recent advances in the study of transcription factors, signaling molecules and regulatory pathways controlling thyroid differentiation and development in the mammalian embryo. Thyroid differentiation of progenitor cells occurs during embryonic development and in the adult thyroid gland, and the molecular bases of these complex and finely regulated processes are becoming ever more clear. 3Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.2Laboratorio de Investigación Aplicada en Enfermedades Neuromusculares, Unidad de Patología Neuromuscular, Servicio de Neuropediatría, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain.1Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC) y Universidad Autónoma de Madrid (UAM), Madrid, Spain.Arístides López-Márquez 1,2, Carlos Carrasco-López 1,3, Celia Fernández-Méndez 1 and Pilar Santisteban 1,3*