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Molecular and Cellular Biology, December 2004, p. 10835-10843, Vol. 24, No. 24
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.24.10835-10843.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Nuclear Orphan Receptor COUP-TFII Is Required for Limb and Skeletal Muscle Development

Christopher T. Lee,1 Luoping Li,1 Norio Takamoto,1 James F. Martin,2 Francesco J. DeMayo,1,3 Ming-Jer Tsai,1,3* and Sophia Y. Tsai1,3*

Department of Molecular and Cellular Biology,1 Program in Developmental Biology, Baylor College of Medicine,3 Alkek Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas2

Received 28 January 2004/ Returned for modification 12 March 2004/ Accepted 9 September 2004

The nuclear orphan receptor COUP-TFII is widely expressed in multiple tissues and organs throughout embryonic development, suggesting that COUP-TFII is involved in multiple aspects of embryogenesis. Because of the early embryonic lethality of COUP-TFII knockout mice, the role of COUP-TFII during limb development has not been determined. COUP-TFII is expressed in lateral plate mesoderm of the early embryo prior to limb bud formation. In addition, COUP-TFII is also expressed in the somites and skeletal muscle precursors of the limbs. Therefore, in order to study the potential role of COUP-TFII in limb and skeletal muscle development, we bypassed the early embryonic lethality of the COUP-TFII mutant by using two methods. First, embryonic chimera analysis has revealed an obligatory role for COUP-TFII in limb bud outgrowth since mutant cells are unable to contribute to the distally growing limb mesenchyme. Second, we used a conditional-knockout approach to ablate COUP-TFII specifically in the limbs. Loss of COUP-TFII in the limbs leads to hypoplastic skeletal muscle development, as well as shorter limbs. Taken together, our results demonstrate that COUP-TFII plays an early role in limb bud outgrowth but not limb bud initiation. Also, COUP-TFII is required for appropriate development of the skeletal musculature of developing limbs.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone for M.-J. Tsai: (713) 798-6253. Fax: (713) 798-8227. E-mail: mtsai{at}bcm.tmc.edu. Phone for S. Y. Tsai: (713) 798-6251. Fax: (713) 798-8227. E-mail: stsai{at}bcm.tmc.edu.

Molecular and Cellular Biology, December 2004, p. 10835-10843, Vol. 24, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.24.10835-10843.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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