Neuronal outgrowth occurs via coordinated remodeling of the cytoskeleton involving both actin and microtubules. Microtubule stabilization drives the extending neurite, yet little is known of the molecular mechanisms whereby extracellular cues regulate microtubule dynamics. Bone morphogenetic proteins (BMPs) play an important role in neuronal differentiation and morphogenesis, and BMP7 in particular induces the formation of dendrites. Here, we show that BMP7 induces stabilization of microtubules in both a MAP2-dependent neuronal cell culture model and in dendrites of primary cortical neurons. BMP7 rapidly activates c-Jun N-terminal kinases (JNKs), known regulators of microtubule dynamics, and we show that JNKs associate with the carboxy terminus of the BMP receptor, BMPRII. Activation and binding of JNKs to BMPRII is required for BMP7-induced microtubule stabilization and for BMP7-mediated dendrite formation in primary cortical neurons. These data indicate that BMPRII acts as a scaffold to localize and coordinate cytoskeletal remodeling and thereby provides an efficient means for extracellular cues, such as BMPs, to control neuronal dendritogenesis.Neurons are highly polarized cells comprised of a single long axon, which transmits signals, and multiple shorter dendrites, which are specialized to receive signals. This polarized property of neurons allows for the establishment of appropriate connections within the central nervous system and ensures unidirectional signal propagation (15, 52). Dendrite formation is critical for normal mammalian brain function, including cognition and memory formation, and dendritic abnormalities closely correlate with mental retardation and underlie the pathology of a number of central nervous system disorders, including Down's, Rett, and Fragile X syndromes and lissencephalies (28,30). Although the importance of dendrite morphology is easily appreciated, the signaling mechanisms by which dendrites develop have only recently begun to be identified (2, 4, 5).Neurite outgrowth occurs as a result of coordinated remodeling of the neuronal cytoskeleton involving actin and microtubules (25). In general, neurite outgrowth occurs as a result of local actin instability in the growth cone and coordinated microtubule stabilization that allows microtubules to protrude their dynamic ends more distally (52). Extracellular growth factors have the ability to regulate the cytoskeleton by activating signaling pathways that change the activity, localization, and stability of cytoskeletal regulators (16). However, the molecular mechanisms by which extracellular factors modulate microtubule stability during dendrite formation remain unclear. c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family with a well-documented role in the regulation of gene transcription, cell death, and survival (9, 50). In the nervous system, JNKs have essential functions in the brain during development, neurite formation, regeneration, and memory formation (27,47). Moreover, accumulating evide...