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Mol Cell January 1, 2001; 7 (1): 137-49.

Two-step regulation of left-right asymmetric expression of Pitx2: initiation by nodal signaling and maintenance by Nkx2.

Shiratori H , Sakuma R , Watanabe M , Hashiguchi H , Mochida K , Sakai Y , Nishino J , Saijoh Y , Whitman M , Hamada H .

Pitx2 is left--right (L--R) asymmetrically expressed initially in the lateral plate and later in primordial visceral organs. The transcriptional regulatory mechanisms that underlie L--R asymmetric expression of Pitx2 were investigated. Mouse Pitx2 has a left side-specific enhancer (ASE) that mediates both the initiation and maintenance of L--R asymmetric expression. This element contains three binding sites for the transcription factor FAST. The FAST binding sites function as Nodal-responsive elements and are sufficient for the initiation but not for the maintenance of asymmetric expression. The maintenance requires an Nkx2-5 binding site also present within the ASE. These results suggest that the left-sided expression of Pitx2 is directly initiated by Nodal signaling and is subsequently maintained by Nkx2. Such two-step control may represent a general mechanism for gene regulation during development.

PubMed ID: 11172719
Article link: Mol Cell

Species referenced: Xenopus laevis
Genes referenced: arsl nodal nodal1 pitx2