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PMID: 12070080 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Eya1 is required for the morphogenesis of mammalian thymus, parathyroid and thyroid.

Development (Cambridge, England) ·Vol. 129 ·No. 13 ·2002-07-00 ·Pages 3033-44

Xu PX, Zheng W, Laclef C, Maire P, Maas RL, Peters H, Xu X

Abstract

Eyes absent (Eya) genes regulate organogenesis in both vertebrates and invertebrates. Mutations in human EYA1 cause congenital Branchio-Oto-Renal (BOR) syndrome, while targeted inactivation of murine Eya1 impairs early developmental processes in multiple organs, including ear, kidney and skeletal system. We have now examined the role of Eya1 during the morphogenesis of organs derived from the pharyngeal region, including thymus, parathyroid and thyroid. The thymus and parathyroid are derived from 3rd pharyngeal pouches and their development is initiated via inductive interactions between neural crest-derived arch mesenchyme, pouch endoderm, and possibly the surface ectoderm of 3rd pharyngeal clefts. Eya1 is expressed in all three cell types during thymus and parathyroid development from E9.5 and the organ primordia for both of these structures failed to form in Eya1(-/-) embryos. These results indicate that Eya1 is required for the initiation of thymus and parathyroid gland formation. Eya1 is also expressed in the 4th pharyngeal region and ultimobranchial bodies. Eya1(-/-) mice show thyroid hypoplasia, with severe reduction in the number of parafollicular cells and the size of the thyroid lobes and lack of fusion between the ultimobranchial bodies and the thyroid lobe. These data indicate that Eya1 also regulates mature thyroid gland formation. Furthermore, we show that Six1 expression is markedly reduced in the arch mesenchyme, pouch endoderm and surface ectoderm in the pharyngeal region of Eya1(-/-) embryos, indicating that Six1 expression in those structures is Eya1 dependent. In addition, we show that in Eya1(-/-) embryos, the expression of Gcm2 in the 3rd pouch endoderm is undetectable at E10.5, however, the expression of Hox and Pax genes in the pouch endoderm is preserved at E9.5-10.5. Finally, we found that the surface ectoderm of the 3rd and 4th pharyngeal region show increased cell death at E10.5 in Eya1(-/-) embryos. Our results indicate that Eya1 controls critical early inductive events involved in the morphogenesis of thymus, parathyroid and thyroid.

MeSH Terms
Animals Apoptosis/genetics Branchial Region/embryology,pathology DNA-Binding Proteins/genetics Ectoderm/metabolism Endoderm/metabolism Gene Expression Regulation, Developmental Homeodomain Proteins/genetics,metabolism Intracellular Signaling Peptides and Proteins Mesoderm Mice Mice, Inbred Strains Mice, Mutant Strains Morphogenesis Neuropeptides/genetics,metabolism Nuclear Proteins PAX9 Transcription Factor Paired Box Transcription Factors Parathyroid Glands/embryology Protein Tyrosine Phosphatases Thymus Gland/embryology Thyroid Gland/embryology Trans-Activators/genetics,metabolism Transcription Factors/genetics
Chemicals
DNA-Binding Proteins HOXB1 homeodomain protein Homeodomain Proteins Intracellular Signaling Peptides and Proteins Neuropeptides Nuclear Proteins PAX9 Transcription Factor Paired Box Transcription Factors Six1 protein, mouse Trans-Activators Transcription Factors PAX1 transcription factor Eya1 protein, mouse Protein Tyrosine Phosphatases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Xu Pin-Xian
McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT 59405, USA. [email protected]
Zheng Weiming
Laclef Christine
Maire Pascal
Maas Richard L
Peters Heiko
Xu Xin
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
0950-1991
Email
[email protected]
Published
2002-07-00
Pages
3033-44
Language
English
Region
England
NLM ID
8701744
PMCID
PMC3873877
Subset
IM
Grants
NCRR NIH HHS · P20 RR015583 · United States
NCRR NIH HHS · P20RR 12345-02 · United States
External Links
PubMed source PMC Full Text View journal details
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