Differential effects of NGF and NT-3 on embryonic trigeminal axon growth patterns

Ulupinar, Emel; Jacquin, Mark F.; Erzurumlu, Reha S.

doi:10.1002/1096-9861(20000918)425:2<202::aid-cne4>3.0.co;2-t

Cited by 50 publications

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“…Exogenous application of NGF and NT-3 to these cultures has differential effects on growth parameters of central trigeminal axons in the brainstem. In the presence of NGF, TG axons leave the central trigeminal tract and extend into the surrounding brainstem tissue without branching, whereas NT-3 promotes precocious arborization of tract axons (Ulupinar et al, 2000a). Localized application of neurotrophins also yields similar results .…”

Section: Introductionmentioning

confidence: 79%

“…However, when NGF is added to the SFM, many axons grow outside the tract and elongate medially or laterally within the brainstem (n = 8; Fig. 2C; see also Ulupinar et al, 2000a). Quantitative and statistical analyses also indicated that there is more growth medially than laterally within the brainstem explants (Fig.…”

Section: Effects Of Ngf On Central Trigeminal Axon Growth Patternsmentioning

confidence: 85%

“…In wholemount cultures derived from E15 rats, most tissue-specific characteristics of the trigeminal pathway are retained. However, central trigeminal axons do not follow the in vivo differentiation rate, rather, they remain restricted to the central trigeminal, without any collateral branching or arborization during a 3-5-day culture period (Ulupinar et al, 2000a; see also Fig. 2A).…”

Section: Effects Of Ngf On Central Trigeminal Axon Growth Patternsmentioning

confidence: 99%

“…Recent studies also suggest that neurotrophins play a major role in axonal differentiation (Hoyle et al, 1993;Lentz et al, 1999;Ulupinar et al, 2000a; see also Gallo and Letourneau, 2000, for a review). During axonal development, elongation and retraction of growth cones are all related to the arrangement of actin cytoskeleton (for reviews, see Lin et al, 1994;Hall, 1998;Gallo and Letourneau, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…1A). Wholemount explants were then cultured on microporous Millicell membranes (Millipore, Bedford, MA) and grown in serum-free culture medium (SFM) at 33°C in a humidified CO 2 incubator (Ulupinar et al, 2000a). …”

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Regulation of neurotrophin‐induced axonal responses via Rho GTPases

Özdinler

Erzurumlu

2001

J of Comparative Neurology

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Nerve growth factor (NGF) and related neurotrophins induce differential axon growth patterns from embryonic sensory neurons. In wholemount explant cultures of embryonic rat trigeminal ganglion and brainstem or in dissociated cell cultures of the trigeminal ganglion, exogenous supply of NGF leads to axonal elongation, whereas neurotrophin-3 (NT-3) treatment leads to short branching and arborization. Axonal responses to neurotrophins might be mediated via the Rho GTPases. To investigate this possibility, we prepared wholemount trigeminal pathway cultures from E15 rats. We infected the ganglia with recombinant vaccinia viruses that express GFP-tagged dominant negative Rac, Rho, or constitutively active Rac or treated the cultures with lysophosphatitic acid (LPA) to activate Rho. We then examined axonal responses to NGF by use of the lipophilic tracer DiI. Rac activity induced longer axonal growth from the central trigeminal tract, whereas the dominant negative construct of Rac eliminated NGF-induced axon outgrowth. Rho activity also significantly reduced, and the Rho dominant negative construct increased, axon growth from the trigeminal tract. Similar alterations in axonal responses to NT-3 and brainderived neurotrophic factor were also noted. Our results demonstrate that Rho GTPases play a major role in neurotrophin-induced axonal differentiation of embryonic trigeminal axons. KeywordsRac; Rho; trigeminal axon growth; NGF; BDNF; viral vectors Primary sensory neurons of the dorsal root and trigeminal (TG) ganglia depend on targetreleased neurotrophins for survival and express specific Trk receptors (McMahon et al., 1994;Wright and Snider, 1995;Conover and Yancopoulos, 1997;Davies, 1997, Davies, 1998Enokido et al., 1999;Huang et al., 1999b). Recent studies also suggest that neurotrophins play a major role in axonal differentiation (Hoyle et al., 1993;Lentz et al., 1999;Ulupinar et al., 2000a; see also Gallo and Letourneau, 2000, for a review). During axonal development, elongation and retraction of growth cones are all related to the arrangement of actin cytoskeleton (for reviews, see Lin et al., 1994;Hall, 1998;Gallo and Letourneau, 2000). The Rho family of GTPases is known to play a major role in this process (for reviews, see Luo et al., 1997;Tapon and Hall, 1997; Aspenstrom, 1999;Mueller, 1999;Song and Poo, 1999;Bishop and Hall, 2000).Members of the family (Cdc42, Rho, and Rac) are either found in the GTP-bound active state or the GDP-bound inactive state (for reviews, see Van Aelst and D'Souza-Schorey, 1997;Mackay and Hall, 1998;Hall 1999;Kjoller and Hall 1999;Bishop and Hall, 2000). Relative abundance of active Rho and Rac might regulate growth cone behavior during axon navigation (Mueller, 1999). Dominant negative and constitutively active versions of Rho GTPases have been used to study their role in axonal arborization (Threadgill et al., 1997;Nakayama et al., 2000), dendritic growth (Threadgill et al., 1997; Ruchoeft et al., 1999;Nakayama et al., 2000;Li et al., 2000), neuronal remodeling (Luo e...

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Section: Introductionmentioning

confidence: 79%

Section: Effects Of Ngf On Central Trigeminal Axon Growth Patternsmentioning

confidence: 85%

Section: Effects Of Ngf On Central Trigeminal Axon Growth Patternsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of neurotrophin‐induced axonal responses via Rho GTPases

Özdinler

Erzurumlu

2001

J of Comparative Neurology

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Morphometric analysis of embryonic rat trigeminal neurons treated with different neurotrophins

Ulupinar¹,

Unal²,

Erzurumlu³

2004

Anat. Rec.

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In whole-mount explant cultures of the trigeminal ganglion (TG) with intact peripheral and brainstem targets, exogenous application of nerve growth factor (NGF) and neurotrophin-3 (NT-3) leads to elongation and precocious arborization of embryonic trigeminal axons, respectively. In addition, neurotrophins play a major role in survival and differentiation of distinct classes of TG neurons. In the present study, we conducted morphometric analyses of trigeminal neurons exposed to exogenous NGF or NT-3 in whole-mount explant cultures. Explants dissected from embryonic day (E) 13 and E15 rats were cultured in the presence of serum-free medium (SFM) or in SFM supplemented with NGF or NT-3 for 3 days. TG neurons were then retrogradely labeled with lipophilic tracer DiI and their soma size distributions were compared following different treatments. The mean diameters of E13 and E15 trigeminal neurons grown in the presence of NT-3 were similar to those grown in SFM. On the other hand, in cultures supplemented with NGF, the mean diameters of neurons were larger at E13, but smaller at E15. Double immunolabeling with TrkA and TrkC antibodies confirmed the presence of large-diameter TrkA-positive neurons in E13 TG, but not in E15 TG. At both ages, other large-diameter neurons expressed only TrkC. These results show that exposure to NGF leads to phenotypic changes in TrkA-expressing trigeminal neurons at early embryonic development, but selective survival of small diameter neurons at later ages. Anat

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Molecular determinants of the face map development in the trigeminal brainstem

2006

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The perception of external sensory information by the brain requires highly ordered synaptic connectivity between peripheral sensory neurons and their targets in the central nervous system. Since the discovery of the whisker-related barrel patterns in the mouse cortex, the trigeminal system has become a favorite model for study of how its connectivity and somatotopic maps are established during development. The trigeminal brainstem nuclei are the first CNS regions where whisker-specific neural patterns are set up by the trigeminal afferents that innervate the whiskers. In particular, barrelette patterns in the principal sensory nucleus of the trigeminal nerve provide the template for similar patterns in the face representation areas of the thalamus and subsequently in the primary somatosensory cortex. Here, we describe and review studies of neurotrophins, multiple axon guidance molecules, transcription factors, and glutamate receptors during early development of trigeminal connections between the whiskers and the brainstem that lead to emergence of patterned face maps. Studies from our laboratories and others' showed that developing trigeminal ganglion cells and their axons depend on a variety of molecular signals that cooperatively direct them to proper peripheral and central targets and sculpt their synaptic terminal fields into patterns that replicate the organization of the whiskers on the muzzle. Similar mechanisms may also be used by trigeminothalamic and thalamocortical projections in establishing patterned neural modules upstream from the trigeminal brainstem. The somatotopic map forms sequentially, beginning at the periphery and ending in the primary somatosensory cortex. In some species, such as rodents, neural modules form within the CNS body maps that correspond to patterned distribution of the sensory receptors in the periphery. In the mouse and rat muzzle, whiskers and sinus hairs are patterned in discrete arrays with constant numbers in each row of follicles (Yamakado and Yohro, 1979;Dörfl, 1985;Rice et al., 1986Rice et al., , 1993Brecht et al., 1997). The infraobital nerve (ION) of the trigeminal ganglion (TG) innervates the whisker pad and relays the whiskerrelated information to the principal sensory nucleus (PrV) in the brainstem, which in turn conveys the signals to the thalamus and the cortex via ascending afferents. The trigeminal brainstem complex also contains the spinal trigeminal nucleus, including subnuclei oralis (SpVo), inter-*Correspondence to: Reha S. Erzurumlu,

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Differential effects of NGF and NT-3 on embryonic trigeminal axon growth patterns

Cited by 50 publications

References 78 publications

Regulation of neurotrophin‐induced axonal responses via Rho GTPases

Regulation of neurotrophin‐induced axonal responses via Rho GTPases

Morphometric analysis of embryonic rat trigeminal neurons treated with different neurotrophins

Molecular determinants of the face map development in the trigeminal brainstem

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