PMID:14695375

Citation	Ozaki, H, Nakamura, K, Funahashi, J, Ikeda, K, Yamada, G, Tokano, H, Okamura, HO, Kitamura, K, Muto, S, Kotaki, H, Sudo, K, Horai, R, Iwakura, Y and Kawakami, K (2004) Six1 controls patterning of the mouse otic vesicle. Development 131:551-62
Abstract	Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is expressed in otic vesicles, nasal epithelia, branchial arches/pouches, nephrogenic cords, somites and a limited set of ganglia. In this study, we established Six1-deficient mice and found that development of the inner ear, nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient embryos were devoid of inner ear structures, including cochlea and vestibule, while their endolymphatic sac was enlarged. The inner ear anomaly began at around E10.5 and Six1 was expressed in the ventral region of the otic vesicle in the wild-type embryos at this stage. In the otic vesicle of Six1-deficient embryos, expressions of Otx1, Otx2, Lfng and Fgf3, which were expressed ventrally in the wild-type otic vesicles, were abolished, while the expression domains of Dlx5, Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally. Our results indicate that Six1 functions as a key regulator of otic vesicle patterning at early embryogenesis and controls the expression domains of downstream otic genes responsible for respective inner ear structures. In addition, cell proliferation was reduced and apoptotic cell death was enhanced in the ventral region of the otic vesicle, suggesting the involvement of Six1 in cell proliferation and survival. In spite of the similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of Six1 and Shh were mutually independent.
Links	PubMed Online version:10.1242/dev.00943
Keywords	Animals; Apoptosis/genetics; Apoptosis/physiology; Body Patterning/physiology; Cell Division/genetics; Cell Division/physiology; Ear, Inner/abnormalities; Ear, Inner/embryology; Ear, Inner/metabolism; Ear, Middle/abnormalities; Ear, Middle/embryology; Ear, Middle/metabolism; Hedgehog Proteins; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Kidney/embryology; Mice; Muscle, Skeletal/embryology; Nose/embryology; Signal Transduction/physiology; Thymus Gland/embryology; Trans-Activators/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:HMX3		GO:0043583: ear development	ECO:0000315:		P		Figure 2. Defects in the inner and middle ear in Six1-deficient mice.	complete CACAO 3403
MOUSE:HMX3	involved_in	GO:0043583: ear development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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