FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2012366768> ?p ?o ?g. }

• W2012366768 endingPage "438" @default.
• W2012366768 startingPage "436" @default.
• W2012366768 abstract "Voluntary motor control requires circuits in the brain to develop synchronously with spinal motor circuitry. In this issue of Developmental Cell, Reimer et al., 2013Reimer M.M. Norris A. Ohnmacht J. Patani R. Zhong Z. Dias T.B. Scott A.L. Chen Y.-C. Rozov S. Frazer S.L. et al.Dev. Cell. 2013; 25 (this issue): 478-491Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar demonstrate that this process is coordinated in zebrafish: dopamine released from descending projections modulates formation of motor neurons by attenuating the response of progenitors to Shh signaling. Voluntary motor control requires circuits in the brain to develop synchronously with spinal motor circuitry. In this issue of Developmental Cell, Reimer et al., 2013Reimer M.M. Norris A. Ohnmacht J. Patani R. Zhong Z. Dias T.B. Scott A.L. Chen Y.-C. Rozov S. Frazer S.L. et al.Dev. Cell. 2013; 25 (this issue): 478-491Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar demonstrate that this process is coordinated in zebrafish: dopamine released from descending projections modulates formation of motor neurons by attenuating the response of progenitors to Shh signaling. The formation of functional motor circuits is a remarkably complex process that requires the coordinated development of spatially distinct neuronal populations within the brain and spinal cord. The realization of executive motor control requires neurons from the brain to project axons over long distances, while the spinal motor neuron (MN) targets must be both present and prepared to receive these descending inputs. Although significant progress has been made toward understanding the local intrinsic and extrinsic factors that give rise to these populations at the appropriate place and time, remarkably little is known about the signals that synchronize their development. In this issue of Developmental Cell, Reimer et al., 2013Reimer M.M. Norris A. Ohnmacht J. Patani R. Zhong Z. Dias T.B. Scott A.L. Chen Y.-C. Rozov S. Frazer S.L. et al.Dev. Cell. 2013; 25 (this issue): 478-491Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar shed light on this question by showing that neurons within the diencephalon promote the generation of their spinal MN targets using the neurotransmitter dopamine. The dopaminergic diencephalospinal tract (DDT) is an ancient and highly conserved component of the vertebrate dopaminergic system found in lampreys, jawed fish, and mammals (Tay et al., 2011Tay T.L. Ronneberger O. Ryu S. Nitschke R. Driever W. Nat Commun. 2011; 2: 171Crossref PubMed Scopus (216) Google Scholar; Lambert et al., 2012Lambert A.M. Bonkowsky J.L. Masino M.A. J. Neurosci. 2012; 32: 13488-13500Crossref PubMed Scopus (108) Google Scholar). Previous studies in zebrafish have shown that the DDT is necessary for proper locomotor development and provides the developing spinal cord with its only source of dopamine at 2 days postfertilization (dpf), a stage that coincides with the generation of spinal MNs (McLean and Fetcho, 2004McLean D.L. Fetcho J.R. J. Comp. Neurol. 2004; 480: 38-56Crossref PubMed Scopus (213) Google Scholar; Tay et al., 2011Tay T.L. Ronneberger O. Ryu S. Nitschke R. Driever W. Nat Commun. 2011; 2: 171Crossref PubMed Scopus (216) Google Scholar; Lambert et al., 2012Lambert A.M. Bonkowsky J.L. Masino M.A. J. Neurosci. 2012; 32: 13488-13500Crossref PubMed Scopus (108) Google Scholar). Given these observations, Reimer et al., 2013Reimer M.M. Norris A. Ohnmacht J. Patani R. Zhong Z. Dias T.B. Scott A.L. Chen Y.-C. Rozov S. Frazer S.L. et al.Dev. Cell. 2013; 25 (this issue): 478-491Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar utilized loss- and gain-of-function strategies to examine the role of dopamine in MN development. Dopamine inputs were removed as follows: (1) inhibiting dopamine synthesis through morpholino-based knockdown of tyrosine hydroxylase 1 (TH1), an enzyme that catalyzes dopamine synthesis; (2) mutating orthopedia1a, a transcription factor essential for the development of the dopaminergic neurons in the DDT; and (3) reducing the number of dopaminergic neurons using the dopamine-specific neurotoxin 6-hydroxydopamine (6-OHDA). In all experiments, reducing dopaminergic input to the spinal cord decreased MN formation, leading to defects in the escape response of larvae at 4 dpf and decreased mobility at 9 dpf. Conversely, the addition of the dopamine agonist peroglide increased MN formation. Together, these experiments reveal that dopamine from the descending DDT promotes the generation of MNs within the developing spinal cord. Next, Reimer et al., 2013Reimer M.M. Norris A. Ohnmacht J. Patani R. Zhong Z. Dias T.B. Scott A.L. Chen Y.-C. Rozov S. Frazer S.L. et al.Dev. Cell. 2013; 25 (this issue): 478-491Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar show that the effects of dopamine on MN generation are principally mediated by the D4a receptor present in Olig2+ MN progenitors (pMN). Interestingly, D4a knockdown not only reduced Hb9+ MN formation but also increased the number of Vsx1+ V2 interneurons. Conversely, the application of dopamine agonists significantly increased the number of pMN cells while blocking V2 interneuron formation. These changes are reminiscent of those observed after manipulating the Sonic hedgehog (Shh) signaling pathway (Ribes and Briscoe, 2009Ribes V. Briscoe J. Cold Spring Harb. Perspect. Biol. 2009; 1: a002014Crossref Scopus (155) Google Scholar), leading the authors to hypothesize that dopamine produced by descending axons acts directly on MN progenitors to heighten their response to Shh and increase their proliferative capacity (Figure 1). Supporting this model, D4a is a member of the D2 class of dopamine receptors that are defined by their inhibition of adenylyl cyclase and corresponding ability to reduce cyclic AMP (cAMP) production. Because cAMP levels influence the activity of the Shh pathway (Hammerschmidt et al., 1996Hammerschmidt M. Serbedzija G.N. McMahon A.P. Genes Dev. 1996; 10: 2452-2461Crossref PubMed Scopus (189) Google Scholar), the observed effects of dopamine on progenitor patterning may result from an elevation of Shh signaling due to suppression of PKA activity. Consistent with this idea, the authors show that peroglide addition stimulates the expression of the Shh target gene Ptch2, and the increase in MN formation can be negated by coadministrating inhibitors of phosphodiesterase IV that elevate cAMP levels. Moreover, the effects of peroglide can be recapitulated by the addition of drugs that directly block adenylyl cyclase activity and reduce cAMP levels. Dopamine from the DDT is thus essential for the generation of spinal MNs and functional locomotor circuits in the developing zebrafish, but does it have a role in the adult spinal cord? Unlike mammals, zebrafish have the ability to regenerate their motor circuitry after spinal lesions (Reimer et al., 2008Reimer M.M. Sörensen I. Kuscha V. Frank R.E. Liu C. Becker C.G. Becker T. J. Neurosci. 2008; 28: 8510-8516Crossref PubMed Scopus (195) Google Scholar). Remarkably, Reimer et al., 2013Reimer M.M. Norris A. Ohnmacht J. Patani R. Zhong Z. Dias T.B. Scott A.L. Chen Y.-C. Rozov S. Frazer S.L. et al.Dev. Cell. 2013; 25 (this issue): 478-491Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar show that the renewed generation of MNs results, in part, from the reactivation of Shh signaling by dopamine in the region rostral to the lesion site. The region caudal to the lesion, however, exhibited reduced regenerative capacity. Arguing that the caudal injury site failed to receive dopamine because it was physically separated from the brain, the authors were able to rescue MN regeneration by applying dopaminergic agonists to the caudal lesion. These results together suggest that dopamine synthesized in the brain is released into the adult spinal cord upon injury to stimulate the generation of new MNs in a manner that recapitulates the events seen in the developing spinal cord. This study provides important new insights into the role of descending dopaminergic projections enhancing spinal MN development and regeneration, and, in turn, raises many questions. First, the DDT is highly conserved in vertebrates; do dopaminergic axon projections similarly stimulate MN generation in the developing mammalian spinal cord? This question awaits further exploration, but previous studies in rodents have suggested that most dopaminergic fibers do not extend into the spinal cord until late embryogenesis and postnatal life (Commissiong, 1983Commissiong J.W. Brain Res. 1983; 264: 197-208Crossref PubMed Scopus (60) Google Scholar), where they play a role modulating the excitability of both spinal interneurons and MNs (Han et al., 2007Han P. Nakanishi S.T. Tran M.A. Whelan P.J. J. Neurosci. 2007; 27: 13192-13204Crossref PubMed Scopus (87) Google Scholar). Second, is the effect of dopamine restricted to promoting pMN identity? It remains unresolved whether the D4a receptors are present solely on pMNs or are more broadly distributed on other groups of spinal progenitors and neurons. Supporting this latter model, dopamine agonists may have more global effects on spinal cord patterning, because they result in the broad expression of Ptch2 throughout the intermediate spinal cord, which is likely to shift cells toward more ventral progenitor identities. Reimer et al., 2013Reimer M.M. Norris A. Ohnmacht J. Patani R. Zhong Z. Dias T.B. Scott A.L. Chen Y.-C. Rozov S. Frazer S.L. et al.Dev. Cell. 2013; 25 (this issue): 478-491Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar elegantly demonstrate that peroglide treatment results in the formation of pMN cells at the expense of the more dorsal p2 population, though the effect on surrounding spinal progenitors remains to be determined. Third, is the action of dopamine restricted to regulating the Shh pathway? cAMP modulates the activities of many developmentally important signaling pathways, including Wnt, BMP, and Notch signaling. Thus, the D4a-mediated reduction of cAMP levels may modulate the generation of different neuronal classes through Shh-independent means. Fourth, do spinal interneurons contribute to the observed motor defects? Increased dopamine signaling may indirectly alter the balance between inhibitory and excitatory control of motor function by specifically affecting the numbers of excitatory V2a or inhibitory V2b interneurons (Batista et al., 2008Batista M.F. Jacobstein J. Lewis K.E. Dev. Biol. 2008; 322: 263-275Crossref PubMed Scopus (66) Google Scholar). Finally, an unexplored aspect of these studies is the identity of the mechanism controlling dopamine release from DDT afferents. Does the DDT have to be electrically active to release dopamine and thereby promote pMN formation and proliferation? If so, when and how does this activity commence in the developing diencephalon? In summary, this study provides intriguing insights into how neuronal populations in the brain and spinal cord synchronize their development to ensure that proper motor circuits are established and repaired. These findings suggest a model in which descending inputs modulate the ability of progenitors to respond to their external environments and, in doing so, actively play a role in stimulating the generation of appropriate neuronal targets from these progenitor populations. Dopamine from the Brain Promotes Spinal Motor Neuron Generation during Development and Adult RegenerationReimer et al.Developmental CellMay 23, 2013In BriefDopaminergic axons descend from the brain and terminate in the spinal cord. Here, Reimer et al. show that dopamine release in the spinal cord promotes the production of motor neurons at the expense of V2 interneurons. This action is mediated by the hedgehog pathway via the D4a receptor. Full-Text PDF Open Archive" @default.
• W2012366768 created "2016-06-24" @default.
• W2012366768 creator A5022243533 @default.
• W2012366768 creator A5047594350 @default.
• W2012366768 creator A5054127025 @default.
• W2012366768 date "2013-06-01" @default.
• W2012366768 modified "2023-09-23" @default.
• W2012366768 title "My Brain Told Me to Do It" @default.
• W2012366768 cites W1989335392 @default.
• W2012366768 cites W2032989177 @default.
• W2012366768 cites W2039829972 @default.
• W2012366768 cites W2042297889 @default.
• W2012366768 cites W2053411111 @default.
• W2012366768 cites W2074791476 @default.
• W2012366768 cites W2092411481 @default.
• W2012366768 cites W2096823486 @default.
• W2012366768 cites W2132610577 @default.
• W2012366768 cites W2144438237 @default.
• W2012366768 doi "https://doi.org/10.1016/j.devcel.2013.05.019" @default.
• W2012366768 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23763945" @default.
• W2012366768 hasPublicationYear "2013" @default.
• W2012366768 type Work @default.
• W2012366768 sameAs 2012366768 @default.
• W2012366768 citedByCount "2" @default.
• W2012366768 countsByYear W20123667682014 @default.
• W2012366768 countsByYear W20123667682017 @default.
• W2012366768 crossrefType "journal-article" @default.
• W2012366768 hasAuthorship W2012366768A5022243533 @default.
• W2012366768 hasAuthorship W2012366768A5047594350 @default.
• W2012366768 hasAuthorship W2012366768A5054127025 @default.
• W2012366768 hasBestOaLocation W20123667681 @default.
• W2012366768 hasConcept C169760540 @default.
• W2012366768 hasConcept C78458016 @default.
• W2012366768 hasConcept C86803240 @default.
• W2012366768 hasConceptScore W2012366768C169760540 @default.
• W2012366768 hasConceptScore W2012366768C78458016 @default.
• W2012366768 hasConceptScore W2012366768C86803240 @default.
• W2012366768 hasIssue "5" @default.
• W2012366768 hasLocation W20123667681 @default.
• W2012366768 hasLocation W20123667682 @default.
• W2012366768 hasOpenAccess W2012366768 @default.
• W2012366768 hasPrimaryLocation W20123667681 @default.
• W2012366768 hasRelatedWork W1828955125 @default.
• W2012366768 hasRelatedWork W1997770566 @default.
• W2012366768 hasRelatedWork W2006264290 @default.
• W2012366768 hasRelatedWork W2034736453 @default.
• W2012366768 hasRelatedWork W2055925137 @default.
• W2012366768 hasRelatedWork W2061542922 @default.
• W2012366768 hasRelatedWork W3048727301 @default.
• W2012366768 hasRelatedWork W4235748225 @default.
• W2012366768 hasRelatedWork W4236969087 @default.
• W2012366768 hasRelatedWork W4250812939 @default.
• W2012366768 hasVolume "25" @default.
• W2012366768 isParatext "false" @default.
• W2012366768 isRetracted "false" @default.
• W2012366768 magId "2012366768" @default.
• W2012366768 workType "article" @default.