Thymus, kidney and craniofacial abnormalities in Six1 deficient mice

• Published in: Mechanisms of development 2003-06, Vol.120 (6), p.669-679
• Main Authors: Laclef, Christine, Souil, Evelyne, Demignon, Josiane, Maire, Pascal
• Format: Article
• Language: English
• Subjects: Dorsal root ganglia; Kidney; Nasal development; Otic placode; Rathke's pouch; Six/sine oculis homeoproteins; Thymus
• ISSN: 0925-4773; 1872-6356
• DOI: 10.1016/S0925-4773(03)00065-0

Six genes are widely expressed during vertebrate embryogenesis, suggesting that they are implicated in diverse differentiation processes. To determine the functions of the Six1 gene, we constructed Six1-deficient mice by replacing its first exon by the β-galactosidase gene. We have previously shown that mice lacking Six1 die at birth due to thoracic skeletal defects and severe muscle hypoplasia affecting most of the body muscles. Here, we report that Six1 −/− neonates also lack a kidney and thymus, as well as displaying a strong disorganisation of craniofacial structures, namely the inner ear, the nasal cavity, the craniofacial skeleton, and the lacrimal and parotid glands. These organ defects can be correlated with Six1 expression in the embryonic primordium structures as revealed by X-Gal staining at different stages of embryogenesis. Thus, the fetal abnormalities of Six1 −/− mice appear to result from the absence of the Six1 homeoprotein during early stages of organogenesis. Interestingly, these Six1 defects are very similar to phenotypes caused by mutations of Eya1, which are responsible for the BOR syndrome in humans. Close comparison of Six1 and Eya1 deficient mice strongly suggests a functional link between these two factors. Pax gene mutations also lead to comparable phenotypes, suggesting that a regulatory network including the Pax, Six and Eya genes is required for several types of organogenesis in mammals.