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

Citation
H. Shiratori et al., Two-step regulation of left-right asymmetric expression of Pitx2: Initiation by nodal signaling and maintenance by Nkx2, MOL CELL, 7(1), 2001, pp. 137-149
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR CELL
ISSN journal
1097-2765 → ACNP
Volume
7
Issue
1
Year of publication
2001
Pages
137 - 149
Database
ISI
SICI code
1097-2765(200101)7:1<137:TROLAE>2.0.ZU;2-0
Abstract
Pitx2 is left-right (L-R) asymmetrically expressed initially in the lateral plate and later in primordial visceral organs. The transcriptional regulat ory mechanisms that underlie L-R asymmetric expression of Pitx2 were invest igated. Mouse Pitx2 has a left side-specific enhancer (ASE) that mediates b oth the initiation and maintenance of L-R asymmetric expression. This eleme nt 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 m aintenance requires an Nkx2-5 binding site also present within the ASE. The se results suggest that the left-sided expression of Pitx2 is directly init iated by Nodal signaling and is subsequently maintained by Nkx2. Such two-s tep control may represent a general mechanism for gene regulation during de velopment.