Local Presentation of Substrate Molecules Directs Axon Specification by Cultured Hippocampal Neurons

Esch, Teresa; Lemmon, Vance; Banker, Gary

doi:10.1523/jneurosci.19-15-06417.1999

Cited by 190 publications

(227 citation statements)

References 46 publications

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“…As expected, a restricted distribution of Tiam1 is also detected in neurons at the stage 2-3 transition; in these cells, Tiam1 preferentially localizes to the minor process displaying the larger growth cone. The small amount of Tiam1 detected in the remaining minor neurites of stage 2 neurons may reflect the potential of all of these processes to become axons (Dotti and Banker, 1987;Esch et al, 1999) or that the sorting machinery is still not fully developed in young Table 3. Effect of cytochalasin D (0.5 g/ml) on axon formation in control and Tiam1-suppressed neurons neurons (Bradke and Dotti, 1997).…”

Section: Discussionmentioning

confidence: 99%

Evidence for the Involvement of Tiam1 in Axon Formation

et al. 2001

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In cultured neurons, axon formation is preceded by the appearance in one of the multiple neurites of a large growth cone containing a labile actin network and abundant dynamic microtubules. The invasion-inducing T-lymphoma and metastasis 1 (Tiam1) protein that functions as a guanosine nucleotide exchange factor for Rac1 localizes to this neurite and its growth cone, where it associates with microtubules. Neurons overexpressing Tiam1 extend several axon-like neurites, whereas suppression of Tiam1 prevents axon formation, with most of the cells failing to undergo changes in growth cone size and in cytoskeletal organization typical of prospective axons. Cytochalasin D reverts this effect leading to multiple axon formation and penetration of microtubules within neuritic tips devoid of actin filaments. Taken together, these results suggest that by regulating growth cone actin organization and allowing microtubule invasion within selected growth cones, Tiam1 promotes axon formation and hence participates in neuronal polarization.

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Section: Discussionmentioning

confidence: 99%

Evidence for the Involvement of Tiam1 in Axon Formation

et al. 2001

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“…Cultured hippocampal neurons tend to form axons preferentially on the substrates coated with extracellular matrix (ECM) component laminin or neuron-glia cell adhesion molecule (NgCAM/L1) than on poly-l-lysine [17,18], suggesting that ECM or cell surface components may serve as extrinsic cues for neuronal polarization. A recent report shows that laminin contact correlates with the emergence of oriented axon of retinal ganglion cells in the zebrafish larvae [16].…”

Section: Introductionmentioning

confidence: 99%

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

et al. 2012

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Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron, but how this increased microtubule stability is achieved is unclear. Here, we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through β1 integrin (Itgb1). Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices. Active Itgb1 was found to be concentrated in laminin-contacting neurites. Axon formation was promoted and abolished by enhancing and attenuating Itgb1 signaling, respectively. Interestingly, laminin contact promoted plus-end microtubule assembly in a manner that required Itgb1. Moreover, stabilizing microtubules partially prevented polarization defects caused by Itgb1 downregulation. Finally, genetic ablation of Itgb1 in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons. Thus, laminin/Itgb1 signaling plays an instructive role in axon initiation and growth, both in vitro and in vivo, through the regulation of microtubule assembly. This study has established a linkage between an extrinsic factor and intrinsic cytoskeletal dynamics during neuronal polarization.

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“…After the adsorption process, the stamp is removed and can be reused for other substrates. Microfluidic patterning provides an advantage over μCP for proteins that do not retain biological activity through the stamping process [112][113][114]. A few investigators have combined μCP and (μFN to simultaneously or sequentially pattern segregated and overlapping fields of different proteins to a single substrate [115,116].…”

Section: Protein μCp Stamping and μFn Depositionmentioning

confidence: 99%

“…Subsequent cell attachment on either of the protein fields may then reveal how cells respond to multiple protein signals in vivo [112,117,118]. In vivo, cells normally form contacts with other cells or with proteins in the extracellular matrix (ECM).…”

Section: Protein Patterns and Cell Choice Assays In Studying Neuronalmentioning

confidence: 99%

“…The patterning techniques including protein film UVor laser ablation [140,141], nitrocellulose paper strip protein transfer [142], microfluidic networks [112,113,143], and microcontact printing [76] have been utilized to produce such substrates. Of interest are studies in which these techniques have been used to generate concentration gradients and protein field boundaries to discover how bound factor density and spatial distrubition affect cell behavior.…”

Section: The Effects Of Cspg Surface Concentrationmentioning

confidence: 99%

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The effects of proteoglycan surface patterning on neuronal pathfinding

Hlady

Hodgkinson

2007

Materialwissenschaft Werkst

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Protein micropatterning techniques are increasingly applied in cell choice assays to investigate fundamental biological phenomena that contribute to the host response to implanted biomaterials, and to explore the effects of protein stability and biological activity on cell behavior for in vitro cell studies. In the area of neuronal regeneration the protein micropatterning and cell choice assays are used to improve our understanding of the mechanisms directing nervous system during development and regenerative failure in the central nervous system (CNS) wound healing environment. In these cell assays, protein micropatterns need to be characterized for protein stability, bioactivity, and spatial distribution and then correlated with observed mammalian cell behavior using appropriate model system for CNS development and repair. This review provides the background on protein micropatterning for cell choice assays and describes some novel patterns that were developed to interrogate neuronal adaptation to inhibitory signals encountered in CNS injuries. Rationale for studying the role of proteoglycans in CNS injuriesNeurons from the central nervous system (CNS) possess a limited capacity to regenerate beyond scar tissue formation barriers in injuries even in the presence of minimal trauma to tissue organization [1,2]. A major culprit in CNS neuronal regenerative failure are the inihibitory proteoglycans (PGs), which are upregulated at the site of CNS injuries. PGs are composed of a core protein with varying numbers of attached glycosaminoglycan (GAG) side chains [3,4]. Proteoglycans are first translated intracellularly into proteins in the endoplasmic reticulum, and then GAG chains are later attached in the Golgi apparatus before secretion into the extracellular space [5][6][7][8]. The study of PGs has particularly been pronounced in the field of neurobiology and development of the nervous system. Numerous studies have concluded that PGs act as barriers that direct the migration of neural crest cells and the outgrowth direction of pathfinding neurons during development [9][10][11][12][13][14][15][16][17]. A number of these studies have additionally shown that cell guidance by PGs is based on an inhibitory signal located within the chondroitin sulfate GAG chains [9,18,19], with the result that the artificial addition of chondroitin sulfate (CS) sugars to the developing nervous system disrupts normal pathfinding [20] as well as does the removal of chondroitin sulfate chains through enzymatic treatment [9,19]. Davies et al. found that chondroitin sulfate proteoglycans (CSPG) are a major constituent of the glial scar and that dorsal root ganglion (DRG) outgrowth termination coincided with an increase in CSPG expression density [21]. Other sources have also shown that CSPGs are upregulated after CNS injuries [22][23][24][25].Interestingly, native adult CNS neurons actually posses the intrinsic ability to regenerate when the wound healing environment is prepared by eliminating inhibitory factors [23,26,27]. In additi...

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Local Presentation of Substrate Molecules Directs Axon Specification by Cultured Hippocampal Neurons

Cited by 190 publications

References 46 publications

Evidence for the Involvement of Tiam1 in Axon Formation

Evidence for the Involvement of Tiam1 in Axon Formation

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

The effects of proteoglycan surface patterning on neuronal pathfinding

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