ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Thyroid. 2020;30:277–289.

GLIS3 gene mutations are associated with a syndrome that combines neonatal diabetes and congenital hypothyroidism due to thyroid dysgenesis [1]. Glis3 knockout mouse models showed functional deficits of thyroid hormone synthesis but were not able to shed light on the role of Glis3 during thyroid organogenesis resulting in thyroid dysgenesis. Rurale et al. close this gap by a systematic developmental study on transient glis3 knockdown in zebrafish embryos during the critical time window of endodermal development and thyroid primordium specification. glis3 knockdown embryos showed developmental defects characterizing thyroid dysgenesis: lower expression of thyroid enriched transcription factors in the endodermal thyroid area, lower number of functional follicles producing thyroxine and lower expression of thyroglobulin. Hypoplasia of the differentiated thyroid tissue was not due to lower rate of proliferation or higher rate of apoptosis in determined thyrocyte precursors. In conclusion, these results provide the first developmental evidence for the key role of GLIS3 for normal thyroid primordium specification and GLIS3 gene defect associated phenotype of thyroid dysgenesis.

Reference:

1. Senee V, Chelala C, Duchatelet S, Feng D, Blanc H, Cossec JC, Charon C, Nicolino M, Boileau P, Cavener DR, Bougneres P, Taha D, Julier C. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nat Genet. 2006;38:682–678.