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First published online September 12, 2006
doi: 10.1242/10.1242/dev.02550

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Arteries define the position of the thyroid gland during its developmental relocalisation

Burkhard Alt^1,*, Osama A. Elsalini^1,*, Pamela Schrumpf^2,*, Nele Haufs², Nathan D. Lawson³, Georg C. Schwabe⁴, Stefan Mundlos⁴, Annette Grüters², Heiko Krude^2, and Klaus B. Rohr^1,

¹ Institute for Developmental Biology, University of Cologne, Gyrhofstrasse 17, 50923 Köln, Germany.
² Institute for Paediatric Endocrinology, Charite University Hospital, Humboldt-University, Berlin, Germany.
³ University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
⁴ Max Planck Institute for Molecular Genetics, Berlin, Germany.

Authors for correspondence [e-mail: heiko.krude{at}charite.de (mouse); klaus.rohr{at}uni-koeln.de (zebrafish)]

Accepted 26 July 2006

During vertebrate development, the thyroid gland undergoes a unique relocalisation from its site of induction to a distant species-specific position in the cervical mesenchyme. We have analysed thyroid morphogenesis in wild-type and mutant zebrafish and mice, and find that localisation of growing thyroid tissue along the anteroposterior axis in zebrafish is linked to the development of the ventral aorta. In grafting experiments, ectopic vascular cells influence the localisation of thyroid tissue cell non-autonomously, showing that vessels provide guidance cues in zebrafish thyroid morphogenesis. In mouse thyroid development, the midline primordium bifurcates and two lobes relocalise cranially along the bilateral pair of carotid arteries. In hedgehog-deficient mice, thyroid tissue always develops along the ectopically and asymmetrically positioned carotid arteries, suggesting that, in mice (as in zebrafish), co-developing major arteries define the position of the thyroid. The similarity between zebrafish and mouse mutant phenotypes further indicates that thyroid relocalisation involves two morphogenetic phases, and that variation in the second phase accounts for species-specific differences in thyroid morphology. Moreover, the involvement of vessels in thyroid relocalisation sheds new light on the interpretation of congenital thyroid defects in humans.

Key words: Thyroid, Zebrafish, Mouse, Arteries, Vegf, Scl, Hedgehog

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