The thyroid anlage develops in the foramen caecum area of the tongue, and migrates through the anterior neck towards its final position in front of the laryngeal cartilages. During migration, the thyroglossal duct, a temporary structure connecting the thyroid anlage and the foramen caecum, is recognized. In the present study, chronological changes and apoptosis in the thyroglossal duct of mice were investigated histochemically using an antibody against Nkx2-1, initially identified as a thyroid transcription factor 1 (ITF1), and the TUNEL reaction in consecutive serial sagittal sections. At embryonic day 10.00 (E10.00), the thyroid anlage was NIcx2-1-immunoreactive and located just below the foramen caecum. As the thyroid anlage descended, the thyroglossal duct was formed at E10.25, being less than 10 mu m in diameter. By E10.75, the Nkx2-1-positive thyroglossal duct had progressively elongated up to 100 mu m. At E11.00 the thyroglossal duct began to disappear, beginning in its mid-portion, and finally became invisible at E11.50. At E11.00-12.00, apoptotic cells were found in an area where the thyroglossal duct was partially discontinuous. After E12.00, cartilaginous tissue of the hyoid bone anlage developed in the mid-portion of the area where the thyroglossal duct had regressed. Immunoreactivity for thyroglobulin, a marker of differentiated thyroid endocrine cells, was detected at E13.00. These results strongly suggest that the mouse thyroglossal duct disappears as a result of apoptosis before differentiation of the endocrine thyroid. (C) 2015 Elsevier GmbH. All rights reserved.