Tbx1 antagonizes thymus organogenesis (86.4)
| Autor: | Kim T. Cardenas, Zhijie Liu, Micheline Laurent, Carla Carter, Nancy Manley, Ellen Richie |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 182:86.4-86.4 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.182.supp.86.4 |
| Popis: | The thymus and parathyroids originate from organ-specific domains in endoderm of the 3rd pharyngeal pouch (PP), identified by Foxn1 and Gcm2 expression respectively at embryonic day 11 (E11). The molecular mechanisms regulating fate determination in the 3rd PP are not clear. Our studies show that neural crest cells (NCCs) play a role in this process (Griffin et al, in press). We also showed that lack of Sonic hedgehog (Shh) results in absence of the parathyroid domain and expansion of the thymus domain (Moore-Scott et al, 2005). It has been proposed that the Tbx1 transcription factor is also required for thymus development and is regulated by Shh. However, Tbx1 is expressed in the Gcm2, but not the Foxn1 domain of 3rd PP at E10.5. We propose a model of thymus organogenesis in which 3rd PP endoderm assumes a thymus fate unless Shh plus NCC-derived signals specify a parathyroid fate. We further propose that Tbx1 is required to establish parathyroid fate and is non-permissive for thymus fate. To test the model, we generated knock-in mice containing a Cre-inducible allele that allows temporal and spatial control of Tbx1 expression. Ectopic Tbx1 expression using Foxn1Cre resulted in markedly hypoplastic thymi, supporting the notion that Tbx1 antagonizes thymus differentiation. Current studies focus on determining the molecular basis for this phenotype and testing the effects of activating Tbx1 expression at earlier stages. Supported by NIH HD056315 to ER and HD035920 to NM. |
| Databáze: | OpenAIRE |
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