RESUMO
Many aspects of the response of Schwann cells to axonal cues can be induced in vitro by the adenylyl cyclase activator forskolin, yet the role of cAMP signaling in regulating Schwann cell differentiation remains unclear. To define better the relationship between cAMP signaling and Schwann cell differentiation, we used a modification of cDNA representational difference analysis (RDA) that permits the analysis of small amounts of mRNA and identified additional genes that are differentially expressed by forskolin-treated and untreated Schwann cells. The genes that we have identified, including MKP3, a regulator of ERK signaling, and the sphingosine-1-phosphate receptor edg3/lp(B3), may play important roles in mediating Schwann cell differentiation.
Assuntos
Colforsina/farmacologia , Proteínas de Ligação a DNA/genética , Proteínas I-kappa B , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Musculares , Proteínas Tirosina Fosfatases/genética , Células de Schwann/fisiologia , Adenosina Trifosfatases/genética , Animais , Axotomia , Células Cultivadas , AMP Cíclico/metabolismo , Fosfatase 6 de Especificidade Dupla , Expressão Gênica/efeitos dos fármacos , Bainha de Mielina/fisiologia , Inibidor de NF-kappaB alfa , Fosfoproteínas/genética , RNA Mensageiro/análise , Ratos , Receptores de Lisofosfolipídeos , Células de Schwann/citologia , Degeneração Walleriana/fisiopatologiaRESUMO
Axon pathfinding relies on the ability of the growth cone to detect and interpret guidance cues and to modulate cytoskeletal changes in response to these signals. We report that the murine POU domain transcription factor Brn-3.2 regulates pathfinding in retinal ganglion cell (RGC) axons at multiple points along their pathways and the establishment of topographic order in the superior colliculus. Using representational difference analysis, we identified Brn-3.2 gene targets likely to act on axon guidance at the levels of transcription, cell-cell interaction, and signal transduction, including the actin-binding LIM domain protein abLIM. We present evidence that abLIM plays a crucial role in RGC axon pathfinding, sharing functional similarity with its C. elegans homolog, UNC-115. Our findings provide insights into a Brn-3.2-directed hierarchical program linking signaling events to cytoskeletal changes required for axon pathfinding.
