Rbms3 function during cartilage formation. (A) Schematic showing how the TGF-βr signaling (Smad-dependent and -independent pathways) affects chondrocyte differentiation (top) and how chondrocytes differentiate from migrating CNC (bottom). Cells not responding to TGF-βr signaling are in shaded gray boxes. Migrating CNC form PCC condensations in the pharyngeal arches. Here, Sox9⁺ (gray) CNC proliferate (black arrow) and receive TGF-β signals (purple), which drives them down the chondrogenic lineage. During development, these cells gradually increase production of Col2a1 (graded red) and reach terminal differentiation. Rbms3 (graded green) is transiently expressed as CNC condense and is gradually excluded from committed chondrocytes. (B) Rbms3 functions to stabilize smad2 transcripts by binding to smad2 3′ utr. This increases/maintains the pool of Smad2 available to receive TGF-βr signaling. Upon Tgf-βr signaling, pSmad2–Smad4 complexes enter the nucleus (Liu, 2003) and bind to Sox9 to: (a) activate transcription of cartilage gene col2a1 (Furumatsu et al., 2005), (b) maintain levels of sox9 (Ito et al., 2003; Wurdak et al., 2005), and (c) repress a battery of other transcription factors (Ito et al., 2003). This drives the PCC to proliferate and commit toward the chondrogenic lineage (Ito et al., 2003; Wurdak et al., 2005).