Theosr1andosr2genes act in the pronephric anlage downstream of retinoic acid signaling and upstream ofwnt2bto maintain pectoral fin development

Abstract

SUMMARYVertebrate odd-skipped related genes (Osr) have an essential function during the formation of the intermediate mesoderm (IM) and the kidney structures derived from it. Here, we show that these genes are also crucial for limb bud formation in the adjacent lateral plate mesoderm (LPM). Reduction of zebrafish Osr function impairs fin development by the failure of tbx5a maintenance in the developing pectoral fin bud. Osr morphant embryos show reduced wnt2b expression, and increasing Wnt signaling in Osr morphant embryos partially rescues tbx5a expression. Thus, Osr genes control limb bud development in a non-cell-autonomous manner, probably through the activation of Wnt2b. Finally, we demonstrate that Osr genes are downstream targets of retinoic acid (RA) signaling. Therefore, Osr genes act as a relay within the genetic cascade of fin bud formation: by controlling the expression of the signaling molecule Wnt2ba in the IM they play an essential function transmitting the RA signaling originated in the somites to the LPM.

Suppression of Bmp4 signaling by the zinc-finger repressors Osr1 and Osr2 is required for Wnt/β-catenin-mediated lung specification in Xenopus

“…Consistent with this possibility, murine Osr1 and Osr2 are partially redundant in joint formation where they regulate Wnt4 and Wnt9b expression (Gao et al, 2011), and Osr2 is required to negatively regulate Bmp4 and Msx1 during tooth development ). Furthermore, we have recently found that, in zebrafish, Osr1/Osr2 also regulates wnt2b expression in lpm during fin development (Neto et al, 2012), suggesting that this regulatory cassette is employed in many tissues.…”

The Polycomb group protein Ring1b is essential for pectoral fin development

“…In response to RA signaling, wnt2ba expression is initiated in the intermediate mesoderm (Ng et al, 2002). In turn, Wnt2ba is required for expression of the T-box transcription factor tbx5 in the lateral plate mesoderm (LPM) (Neto et al, 2012). Between the 6-and 15-somite stages (ss; 12-16 hours post-fertilization, hpf) (Kimmel et al, 1995), tbx5-positive cells comprise two bilateral stripes that contain both heart and fin precursors (Ahn et al, 2002; Begemann RESEARCH ARTICLE Ring1b controls fin development and Ingham, 2000; Furthauer et al, 2001).…”

Early expression of the <i>tbx</i>22 gene in zebrafish influences positioning of pharyngeal arch cartilages

“…In zebrafish osr1 is expressed robustly in the ventral head mesenchyme and branchial arches but its role in craniofacial development has not been examined. Osr1 has been shown to be essential for kidney formation [29], and recently has been shown to interact with tbx5a during pectoral fin development [30]. Here we show that osr1 is severely disrupted by loss of tbx22-2 expression.…”

“…It is more likely that the gdf5 levels are being influenced by another factor independent of bapx1. Osr1 has been shown to be required for maintenance of expression of signaling molecules critical for joint formation, including Gdf5 [30]. This work has also revealed a significant loss of osr1 signaling in tbx22 morphants which positions osr1 as a candidate for mediating the effect of loss of early tbx22 signals in craniofacial development.…”

“…Vertebrate Osr genes are expressed in many tissues and have been shown to be required for proper formation and/or patterning of the heart, endoderm, teeth, palate, the bones and synovial joints in the limbs [28,[32][33][34][35][36]. While no studies have defined the specific requirement of osr1 in zebrafish craniofacial development, recent work has shown that osr1 and tbx5a interact to drive proper formation of the pectoral fins [30].…”