Osteogenic protein-1 induces dendritic growth in rat sympathetic neurons

Abstract

Sympathetic neurons from perinatal rat pups extend only a single axon when maintained in culture in the absence of glia and serum. Exposure to recombinant osteogenic protein-1 (OP-1) selectively induces the formation of dendrites that correctly segregate and modify cytoskeletal and membrane proteins and form synaptic contacts of appropriate polarity. OP-1 requires nerve growth factor (NGF) as a cofactor, and, in the presence of optimal concentrations of NGF, OP-1-induced dendritic growth from cultured perinatal neurons is comparable to that observed in situ. Sympathetic neuroblasts that had not formed dendrites in situ also responded to OP-1 in culture, indicating that OP-1 can cause de novo formation as well as regeneration of dendrites. These data imply that specific signals can regulate the development of neuronal shape and polarity.

Signaling by Bone Morphogenetic Proteins and Smad1 Modulates the Postnatal Differentiation of Cerebellar Cells

“…For example, BMPs trigger neuronal differentiation in cultures prepared from precursors in the ventricular zone at E12-E13 (Li et al, 1998). In cultures of sympathetic neurons, BMP treatment can induce dendritic outgrowth (Lein et al, 1995) and promote synaptotagmin I expression (Patzke et al, 2001), changes consistent with our findings. Brief treatment with BMPs can also induce cultures of neural precursor cells from embryonic mice (Nakashima et al, 2001) or oligodendrocytes from newborn rats (Grinspan et al, 2000) to differentiate into astrocytes.…”

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

“…BMP signaling regulates neurite outgrowth and dendritic development throughout the CNS, including cortical neurons Le Roux et al 1999;Lee-Hoeflich et al 2004;Podkowa et al 2010), hippocampal neurons (Withers et al 2000), and cerebellar neurons (Matsuura et al 2007). In culture, treatment of sympathetic neurons with BMP-2, BMP-5, BMP-6, or BMP-7 enhances dendritic development (Lein et al 1995(Lein et al , 1996Guo et al 1998;Beck et al 2001;Horbinski et al 2002). However, in cerebellar granule neurons, BMP-2 inhibits neurite outgrowth by LIMK-dependent mechanisms (Matsuura et al 2007).…”

The Novel GTPase Rit Differentially Regulates Axonal and Dendritic Growth

“…The most significant difference is that in contrast to hippocampal neurons, sympathetic neurons derived from embryonic rat superior cervical ganglia extend only a single axonal process during the first 24 h in culture, and when these neurons are grown in serum-free medium in the absence of non-neuronal cells, this polarity is maintained for up to 3 months in culture (Bruckenstein and Higgins, 1988). Dendritic growth in sympathetic neurons requires extrinsic cues: coculture with glial cells (Tropea et al, 1988;Lein et al, 2002) or exposure to BMPs in the presence of NGF (Lein et al, 1995) triggers these neurons to form multiple dendrites in addition to a single axon. Thus, to determine whether Rit signaling represents a divergent or convergent mechanism for regulating axonal versus dendritic growth modes in diverse neuronal cell types, we first determined whether Rit is expressed endogenously in sympathetic neurons and then analyzed the effects of manipulating Rit activation on axonal and dendritic growth in sympathetic neurons.…”

“…In this study, we demonstrate that cantly increased numbers of neurons expressing Rit constructs were obtained using adenoviral vectors, this method was used to generate the data presented in Results. Dendritic growth was induced in sympathetic cultures by adding suboptimal (10 ng/ml) or maximally effective (50 ng/ml) concentrations of BMP7 to the culture medium (Lein et al, 1995) within 24 h after exposure to expression vectors. To determine the role of ERK1/2 in Rit effects on neuronal morphogenesis, cultures were treated with MEK inhibitor PD98059.…”

“…To determine the percentage of polarized neurons in hippocampal cultures 48 h after plating, we used a conservative definition of polarization: a neuron was considered to be polarized if its longest neurite was at least 50 m longer than any of its other processes (Lein et al, 1992). Immunocytochemistry was used to distinguish axons from dendrites (Lein et al, 1995). Cultures were fixed with 4% paraformaldehyde, permeabilized with 0.1% Triton-X-100 in PBS, and reacted with polyclonal antibodies that react with GFP (Invitrogen, Eugene, OR) and mAbs that react with either axon-or dendrite-selective antigens.…”