Elsevier

Developmental Biology

Volume 236, Issue 2, 15 August 2001, Pages 316-329
Developmental Biology

Regular Article
Hoxa3 and Pax1 Regulate Epithelial Cell Death and Proliferation during Thymus and Parathyroid Organogenesis

https://doi.org/10.1006/dbio.2001.0342Get rights and content
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Abstract

The thymus and parathyroid glands in mice develop from a thymus/parathyroid primordium that forms from the endoderm of the third pharyngeal pouch. We investigated the molecular mechanisms that promote this unique process in which two distinct organs form from a single primordium, using mice mutant for Hoxa3 and Pax1. Thymic ectopia in Hoxa3+/−Pax1−/− compound mutants is due to delayed separation of the thymus/parathyroid primordium from the pharynx. The primordium is hypoplastic at its formation, and has increased levels of apoptosis. The developing third pouch in Hoxa3+/−Pax1−/− compound mutants initiates normal expression of the parathyroid-specificGcm2 and thymus-specific Foxn1 genes. However, Gcm2 expression is reduced at E11.5 in Pax1−/− single mutants, and further reduced or absent in Hoxa3+/−Pax1−/− compound mutants. Subsequent to organ-specific differentiation from the shared primordium, both the parathyroids and thymus developed defects. Parathyroids in compound mutants were smaller at their formation, and absent at later stages. Parathyroids were also reduced in Pax1−/− mutants, revealing a new function forPax1 in parathyroid organogenesis. Thymic hypoplasia at later fetal stages in compound mutants was associated with increased death and decreased proliferation of thymic epithelial cells. Our results suggest that a Hoxa3–Pax1 genetic pathway is required for both epithelial cell growth and differentiation throughout thymus and parathyroid organogenesis.

Keywords

Hox
Pax
Gcm2
thymus
parathyroid
pharyngeal pouch
endoderm
organogenesis
proliferation
apoptosis

Cited by (0)

1

Current address: Gene Evaluation and Mapping Laboratory, USDA Agricultural Research Center, Beltsville, MD 20705.

2

Current address: Department of Biological Sciences, Alabama State University, Montgomery, AL 36101-2071.

3

To whom correspondence should be addressed. Fax: (706) 721-8685; E-mail: [email protected].