Zebrafish hhex, nk2.1a, and pax2.1 regulate thyroid growth and differentiation downstream of Nodal-dependent transcription factors.
During zebrafish development, the thyroid primordium initiates expression of molecular markers such as hhex and nk2.1a in the endoderm prior to pharynx formation. As expected for an endodermally derived organ, initiation of thyroid development depends on Nodal signalling. We find that it also depends on three downstream effectors of Nodal activity, casanova (cas), bonnie and clyde (bon), and faust (fau)/gata5. Despite their early Nodal-dependent expression in the endoderm, both hhex and nk2.1a are only required relatively late during thyroid development. In hhex and nk2.1a loss-of-function phenotypes, thyroid development is initiated and arrests only after the primordium has evaginated from the pharyngeal epithelium. Thus, like pax2.1, both hhex and nk2.1a have similarly late roles in differentiation or growth of thyroid follicular cells, and here, we show that all three genes act in parallel rather than in a single pathway. Our functional analysis suggests that these genes have similar roles as in mammalian thyroid development, albeit in a different temporal mode of organogenesis.
Institute for Developmental Biology, University of Cologne, Gyrhofstrasse 17, 50923 Köln, Germany.
Osama A
OA
Elsalini
Julia
J
von Gartzen
Matthias
M
Cramer
Klaus B
KB
Rohr
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000502:physiology*; D004707:Endoderm / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D055457:Nodal Protein; D051762:PAX2 Transcription Factor; D012097:Repressor Proteins; D013961:Thyroid Gland / Q000196:embryology*; D014157:Transcription Factors / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; C513080:Hhex protein, mouse; C513077:Hhex protein, zebrafish; D018398:Homeodomain Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C497320:pax2a protein, zebrafish