An integrated regulatory network controlling survival and migration in thyroid organogenesis.
The thyroid gland originates from the ventral floor of the foregut as a thickening of the endodermal cell layer. The molecular mechanisms underlying the early steps of thyroid morphogenesis are not known. Gene targeting experiments have contributed to the identification of several transcription factors, in general playing a role in the proliferation, survival, and migration of the thyroid cell precursors. The experiments reported here analyze the expression of the transcription factors Titf1, Hhex, Pax8, and Foxe1 in the thyroid primordium of null mutants of each of them. We found that most of these transcription factors are linked in an integrated regulatory network, each of them controlling the presence of other members of the network. The expression of Foxe1 is regulated in an intriguing fashion as it is strongly dependent on the presence of Pax8 in thyroid precursor cells, while the expression of the same gene in the pharyngeal endoderm surrounding the primordium is dependent on Sonic hedgehog (Shh)-derived signaling. Moreover, by the generation of mouse mutants expressing Foxe1 exclusively in the thyroid primordium, we provide a better understanding of the role of Foxe1 in these cells in order to acquire the competence to migrate into the underlying mesenchyme. In conclusion, we provide the first evidence of gene expression programs, controlled by a hierarchy of transcription factors expressed in the thyroid presumptive gut domain and directing the progression of thyroid morphogenesis.
Parlato
Rosanna
R
Stazione Zoologica Anton Dohrn, Naples, Italy.
Rosica
Annamaria
A
Rodriguez-Mallon
Alina
A
Affuso
Andrea
A
Postiglione
Maria Pia
MP
Arra
Claudio
C
Mansouri
Ahmed
A
Kimura
Shioko
S
Di Lauro
Roberto
R
De Felice
Mario
M
D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C472789:Foxe1 protein, mouse; D053823:Hedgehog Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; C465570:Shh protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors