Enhanced Neurite Outgrowth in PC12 Cells Mediated by Connexin Hemichannels and ATP

Gap junctions have traditionally been described as transmembrane channels that facilitate intercellular communication via the passage of small molecules. Connexins, the basic building blocks of gap junctions, are expressed in most mammalian tissues including the developing and adult central nervous system. During brain development, connexins are temporally and spatially regulated suggesting they play an important role in the proper formation of the central nervous system. In the current study, connexins 32 and 43 were overexpressed in PC12 cells to determine whether connexins are involved in neuronal differentiation. Both connexin 32 and 43 were appropriately trafficked to the cell membrane following overexpression and resulted in the formation of functional gap junctions. Connexin overexpression was found to cause enhanced neurite outgrowth in PC12 cells treated with nerve growth factor to initiate neuritogenesis. Surprisingly, however, enhanced neurite outgrowth was found to be the consequence of functional hemichannel formation as opposed to traditional intercellular communication. Additional analysis revealed that ATP was released into the media likely through hemichannels and acted on purinergic receptors to cause enhanced neurite outgrowth. Collectively, the results of the current study suggest that connexins may play an important role in neuronal differentiation by non-traditional mechanisms. Gap junctions have traditionally been described as transmembrane channels that facilitate intercellular communication via the passage of small molecules. Connexins, the basic building blocks of gap junctions, are expressed in most mammalian tissues including the developing and adult central nervous system. During brain development, connexins are temporally and spatially regulated suggesting they play an important role in the proper formation of the central nervous system. In the current study, connexins 32 and 43 were overexpressed in PC12 cells to determine whether connexins are involved in neuronal differentiation. Both connexin 32 and 43 were appropriately trafficked to the cell membrane following overexpression and resulted in the formation of functional gap junctions. Connexin overexpression was found to cause enhanced neurite outgrowth in PC12 cells treated with nerve growth factor to initiate neuritogenesis. Surprisingly, however, enhanced neurite outgrowth was found to be the consequence of functional hemichannel formation as opposed to traditional intercellular communication. Additional analysis revealed that ATP was released into the media likely through hemichannels and acted on purinergic receptors to cause enhanced neurite outgrowth. Collectively, the results of the current study suggest that connexins may play an important role in neuronal differentiation by non-traditional mechanisms. Gap junctions form transmembrane channels through the plasma membranes of adjacent cells providing an intercellular link from the cytoplasm of one cell to the next. Traditionally, gap junctions were thought to mediate cell-cell communication through the cytoplasmic exchange of molecules such as Ca2+ and ATP (1Bruzzone R. White T.W. Paul D.L. Eur. J. Biochem. 1996; 238: 1-27Crossref PubMed Scopus (1242) Google Scholar). However, recent studies have shown that gap junctions may serve additional functions within the cell including regulating gene expression and the release of small signaling molecules through hemichannels directly into the extracellular environment (2Goodenough D.A. Paul D.L. Nat. Rev. Mol. Cell. Biol. 2003; 4: 285-295Crossref PubMed Scopus (588) Google Scholar). Gap junctions are composed of oligmerized connexin (Cx) 2The abbreviations used are: Cx, connexin; NGF, nerve growth factor; DMEM, Dulbecco's modified Eagle's medium; PC12, pheochromocytoma; EGFP, enhanced green fluorescent protein; CBX, carbenoxolone; PPADS, pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid); 2-MeSATP, 2-methylthioadenosine triphosphate; PI, propidium iodide; TrkA, tropomyosin receptor kinase A. proteins and more than 20 different mammalian Cx genes have been identified to date (3Sohl G. Willecke K. Cell Commun. Adhes. 2003; 10: 173-180Crossref PubMed Scopus (375) Google Scholar). Cx genes are expressed in most mammalian tissues although not every individual Cx is expressed in every tissue. In the central nervous system, the expression of several different Cx proteins, including Cx26, 29, 30, 32, 36, 43, 45, and 47, has been reported (4Sohl G. Maxeiner S. Willecke K. Nat. Rev. Neurosci. 2005; 6: 191-200Crossref PubMed Scopus (436) Google Scholar, 5Theis M. Sohl G. Eiberger J. Willecke K. Trends Neurosci. 2005; 28: 188-195Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar). In the adult brain, specific Cx proteins tend to be enriched in particular cell types. For example, Cx43 is highly expressed in astrocytes, whereas Cx29 and Cx32 have been found in oligodendrocytes (6Rash J.E. Yasumura T. Davidson K.G. Furman C.S. Dudek F.E. Nagy J.I. Cell Commun. Adhes. 2001; 8: 315-320Crossref PubMed Scopus (180) Google Scholar, 7Nagy J.I. Ionescu A.-V. Lynn B.D. Rash J.E. Glia. 2003; 44: 205-218Crossref PubMed Scopus (162) Google Scholar, 8Altevogt B.M. Kleopa K.A. Postma F.R. Scherer S.S. Paul D.L. J. Neurosci. 2002; 22: 6458-6470Crossref PubMed Google Scholar). Recently, Cx36 and Cx45 were identified as the predominant connexins expressed in adult neurons (9Sohl G. Degen J. Teubner B. Willecke K. FEBS Lett. 1998; 428: 27-31Crossref PubMed Scopus (227) Google Scholar, 10Srinivas M. J. Neurosci. 1999; 19: 9848-9855Crossref PubMed Google Scholar, 11Maxeiner S. Neuroscience. 2003; 119: 689-700Crossref PubMed Scopus (133) Google Scholar). Deletion of either of the adult neuronal Cx genes, Cx36, or Cx45, results in deficiencies in signaling and transmission properties of neurons (12Maxeiner S. Dedek K. J. Neurosci. 2005; 25: 566-576Crossref PubMed Scopus (127) Google Scholar, 13Deans M.R. Volgyi B. Goodenough D.A. Bloomfield S.A. Paul D.L. Neuron. 2002; 36: 703-712Abstract Full Text Full Text PDF PubMed Scopus (345) Google Scholar, 14Frisch C. Behav. Brain Res. 2005; 157: 177-185Crossref PubMed Scopus (101) Google Scholar). In the developing central nervous system, the role of gap junctions in neurons or cells destined to become neurons is less clear. Studies have shown that Cx genes such as Cx32 and Cx43 are highly expressed in the developing brain and that distinct regional and temporal expression patterns are formed by different Cx proteins (15Belliveau D.J. Kidder G.M. Naus C.C. Dev. Genet. 1991; 12: 308-317Crossref PubMed Scopus (45) Google Scholar, 16Belliveau D.J. Naus C.C. Dev. Neurosci. 1995; 17: 81-96Crossref PubMed Scopus (55) Google Scholar, 17Honma S. De S. Li D. Shuler C.F. Turman Jr, J.E. Synapse. 2004; 52: 258-271Crossref PubMed Scopus (23) Google Scholar, 18Leung D.S.Y. Unsicker K. Reuss B. Int. J. Dev. Neurosci. 2002; 20: 63-75Crossref PubMed Scopus (50) Google Scholar, 19Nadarajah B. Jones A.M. Evans W.H. Parnavelas J.G. J. Neurosci. 1997; 17: 3096-3111Crossref PubMed Google Scholar). For example, in the developing neocortex, Cx32 protein expression is most abundant in the later stages of development and found to be localized in areas of myelinated axons and clusters of developing neurons (16Belliveau D.J. Naus C.C. Dev. Neurosci. 1995; 17: 81-96Crossref PubMed Scopus (55) Google Scholar, 19Nadarajah B. Jones A.M. Evans W.H. Parnavelas J.G. J. Neurosci. 1997; 17: 3096-3111Crossref PubMed Google Scholar). Cx43, in contrast, is expressed throughout cortical development in both neurons and radial glia (16Belliveau D.J. Naus C.C. Dev. Neurosci. 1995; 17: 81-96Crossref PubMed Scopus (55) Google Scholar, 19Nadarajah B. Jones A.M. Evans W.H. Parnavelas J.G. J. Neurosci. 1997; 17: 3096-3111Crossref PubMed Google Scholar, 20Bittman K.S. LoTurco J.J. Cereb. Cortex. 1999; 9: 188-195Crossref PubMed Scopus (101) Google Scholar). Radial glia were classically thought to provide a temporary structural framework for neuronal migration. However, recent evidence suggests that radial glia are in fact neuronal progenitor cells that later become excitatory cortical neurons (21Noctor S.C. Flint A.C. Weissman T.A. Dammerman R.S. Kriegstein A.R. Nature. 2001; 409: 714-720Crossref PubMed Scopus (1562) Google Scholar, 22Malatesta P. Hartfuss E. Gotz M. PubMed Google Scholar, P. Hartfuss E. Gotz M. Neuron. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). the extracellular release of ATP via Cx hemichannels in radial glia was shown to cortical progenitor cell T.A. Flint A.C. Kriegstein A.R. Neuron. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). Cx32 and Cx43 were found to be temporally regulated in neurons of the that with the development of the D.S.Y. Unsicker K. Reuss B. Int. J. Dev. Neurosci. 2002; 20: 63-75Crossref PubMed Scopus (50) Google Scholar). Collectively, the results suggest that Cx proteins may play an important role in proper central nervous development including the and development of with the that Cx proteins may play a role in neuronal development, several recent studies in have that connexins and gap junctions neuronal differentiation. For example, and cells be to neurons Int. J. Dev. Biol. Google Scholar, Dev. Biol. PubMed Scopus Google Scholar). Both cell Cx43 and are M. Naus C.C. J. Neurosci. Res. 1997; PubMed Scopus Google Scholar, D.J. K.A. Naus C.C. Dev. Genet. 1997; PubMed Scopus Google Scholar). of and cells with or to channels resulted in a in the of neurons following differentiation M. Naus C.C. 1999; PubMed Scopus Google Scholar, M. Naus C.C. Dev. Genet. 1999; PubMed Google Scholar). the role of Cx genes in neuronal Cx32 and Cx43 were overexpressed in PC12 PC12 cells are cells that be to form neurons following with nerve growth factor S. A. PubMed Scopus Google Scholar). of PC12 cells with cell is that they form neurons and not cell differentiation. they not of Cx32 or Cx43 M. J. Neurosci. 1999; 19: 9848-9855Crossref PubMed Google Scholar, B.D. Nagy J.I. Neurosci. Lett. 1995; PubMed Scopus Google and are with P. P. A. D.J. J. Neurosci. Res. 2005; PubMed Scopus Google Scholar). Cx32 or Cx43 is trafficked appropriately in PC12 cells in functional gap In the current study that expression of Cx32 or Cx43 in PC12 cells resulted in enhanced neurite outgrowth with neurite outgrowth is the consequence of hemichannel formation and the release of ATP into the extracellular the results suggest that Cx genes may play an important role in the of neuronal differentiation. Cell cells from were in with and in a For of the differentiation PC12 cells were treated with in media and and media were every of the and used throughout the study were from were on and was from cell S. A. 1996; PubMed Scopus Google was a from C. cells were in with and in a and of Cx43, and were through of the of into the with the of the was by and to from a Cx, or was as described J. J. J. Naus J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). cells were a of cell and with the of media with of was used the in of PC12 media with of was to the and the cells were in the following the was with PC12 to the cells to to was and every a the was and was by J. P. for J. E. 1997; 8: PubMed Scopus Google Scholar). Cx43 was by E. of and the Cx32 and Cx43 were a from D. of Additional media and was by D. and are to to the membrane appropriately are to form functional Cx43 channels E. D. E. Kidder G.M. J. Biol. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar). of and PC12 cells were a of cells on the to following cells were with EGFP, Cx43, or for and with for Cx32 and Cx43 proteins were with or Cx32 and Cx43 were of the cells were with to and in the of were were from on an of cells the protein was and expressed as a of the of were in the of In to or cells were for Cx32 and Cx43, to determine whether the of and expression of Cx, protein was from PC12 PC12 cells or PC12 cells the Cx protein were used to and for either Cx32 or Cx43 as Cell and of the proteins of were as P. P. A. D.J. J. Neurosci. Res. 2005; PubMed Scopus Google Scholar). and cells were on a of or were and for functional gap Cx43, and or following and cells with Cx32 or Cx43 were with whereas cells with EGFP, or were with an and an was for were following to determine whether from the cell to were to be the cell to one adjacent of cells was as the of cells that by the of of was by the of cells from the to the cell that of PC12 were a of and the following with EGFP, Cx43, or the cells were treated with in and media were every of and neurite was following and and the of the cells were and an and was in of the of cell For of the of a neurite was as an from the cell or than the cell J. 2001; PubMed Scopus Google Scholar, S. T. G. Neuroscience. PubMed Scopus Google Scholar, Neurosci. Lett. 1996; PubMed Scopus (55) Google Scholar). of neurite and the of was by 20 of in were an analysis of by from neurite that overexpression of Cx proteins was to cause of the PC12 neurite outgrowth in PC12 cells with was were with EGFP, Cx43, or and neurite was and following in the the and revealed that cells the Cx proteins were However, analysis of neurite was that PC12 cells from the enhanced neurite outgrowth although of the cells not to Cx as by the the that gap junctions cause enhanced neurite outgrowth by a than intercellular PC12 cells were with EGFP, or the cells were and as of and or and cells were treated with for or and neurite was in and of PC12 with ATP and of the that enhanced neurite outgrowth with Cx overexpression is likely by a factor in the gap junctions are to the passage of ATP and purinergic receptors neurite outgrowth B. S. G. G. C. Neuroscience. 2001; PubMed Scopus Google Scholar, Naus C.C. A.C. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google ATP and were to determine whether they neurite outgrowth. PC12 cells were treated with either ATP or 2-methylthioadenosine to determine whether either purinergic receptor neurite growth in the of For PC12 cells were as and with EGFP, or cells were treated with ATP 2-MeSATP, or of the was with was to the of as as and following of For the the cells were with EGFP, or as was treated with whereas the or pyridoxal phosphate-6-azo(benzene-2,4-disulfonic was to the cells and the of the was to the of and and following of ATP determine whether ATP was released from the ATP were from the media of or cells were treated as described that media the with NGF, the was cell by and the media overexpression of Cx32 and Cx43 in the of by media was from cells and following with the and Cx ATP were an ATP to the analysis was an analysis of by and that ATP opposed to gap was for the of neurite cells were and with EGFP, or media was and the cells were with to media was and the cells were to the media for media was and PC12 cells were as described for the neurite outgrowth studies not media was with media and following the of the media NGF, neurite outgrowth was as an additional was to PC12 cells and neurite was in with the cells to that media not neurite outgrowth. In of the media was treated with to ATP to to the the cells treated with the media were a to that was of and of the PC12 was from additional cells treated with the media and for and expression by not Cx43 that functional Cx hemichannels are for enhanced neurite PC12 cells were with EGFP, or Cx43 as was with either the gap or the is to Cx hemichannels S. J. Neurosci. 2003; PubMed Google Scholar, M. K. T. R. 2001; PubMed Scopus Google Scholar). outgrowth was PC12 cells were with or and neurite outgrowth was and with and cells treated with determine whether Cx overexpression and a functional on propidium were PC12 cells were treated with EGFP, Cx43 media for media was with media for and with media with or for an additional and cells with were and and cells treated and with were was directly to the media for cells were with and a of were a and in were and an analysis of by Cx32 and Cx43 and the of Gap PC12 cells and cells with not of either Cx32 or Cx43 However, PC12 cells with Cx43, or expressed of Cx protein of the with Cx or proteins and to Cx43 or Cx32 revealed abundant and the For example, cells with in the cytoplasm and adjacent cells with or and for Cx43 or Cx32 an that was not of the Cx, or not cause in with the PC12 cells from the enhanced neurite outgrowth described in Cell on the or of or for and cells revealed that the for the used in the current study was the suggests that with Cx results in the expression and of Cx or proteins and that the not the of Cx within the the that the is highly and for Cx in the PC12 determine whether overexpression of Cx43, or proteins results in the formation of functional gap junctions, with or with or was results revealed that and cells were not whereas PC12 cells Cx32 or Cx43 to adjacent results were the cells and results from cells with or were into on whether the cell with expressed the that expressed or were whereas cells that were PC12 cells were following for passage to determine whether and the of PC12 cells functional functional was found following of or Cx43, and cells functional to was in the However, the was in the cells the overexpression of gap junctions in PC12 cells in the of functional in a cell of of Cx32 and Cx43 on of was in the and cells to the of and different stages following were in the or cells following is that overexpression of may have neurite and cells were in a was in neurite EGFP, and PC12 cells following the of to not neurite outgrowth was in the cells to with although the of was was the and of the that from the neurite outgrowth was that of the PC12 cells on the or to have although cells that expressed of by neurite outgrowth was in cells and on the or of the PC12 cells on the enhanced neurite outgrowth with PC12 cells with However, was in neurite and cells following with results were a is that PC12 cells that may have expressed of Cx PC12 cells were with or and with of PC12 cells with or on the enhanced neurite outgrowth with cells on with was the and cells on the with to neurite outgrowth Cx43, and neurite outgrowth and suggests that expression of Cx in PC12 cells results in the release of into the media that are for the enhanced neurite outgrowth. recent studies have shown that purinergic receptors neurite outgrowth and that ATP through gap junctions B. S. G. G. C. Neuroscience. 2001; PubMed Scopus Google Scholar, Naus C.C. A.C. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). a of ATP and were used to determine whether ATP was for the on neurite outgrowth. of the purinergic receptor or to the media the enhanced outgrowth in the PC12 in PC12 cells or and was from cells treated with a small in neurite of and with cells ATP or receptor was to enhanced neurite outgrowth was was cells and ATP cells than PC12 cells that Cx overexpression to a release of ATP into the an ATP media was results that overexpression of either Cx32 or Cx43 results in an in ATP media the of to the media ATP were in the media of and cells to the of a was However, a in ATP were in the media of the cells the neurite outgrowth following Cx been the link ATP released into the media and enhanced neurite media was from and cells and used to PC12 treated with the media and not of Cx32 or Cx43 protein that was of and of the cells not PC12 cells treated with media from the and cells neurite with the media from the cells with ATP the enhanced neurite outgrowth was in neurite PC12 cells treated with media or that media was not a factor not Connexin and neurite outgrowth and ATP that Cx hemichannels were for the release of ATP in the the of Cx the or Cx43 were of CBX, an to Cx hemichannels S. J. Neurosci. 2003; PubMed Google Scholar, M. K. T. R. 2001; PubMed Scopus Google to Cx PC12 enhanced neurite outgrowth. PC12 cells were by as were and Cx PC12 cells treated with the PC12 cells with Cx43 that are of functional Cx including hemichannels E. D. E. Kidder G.M. J. Biol. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar, A. A.C. J. Cell 119: PubMed Scopus Google to enhanced neurite outgrowth following the of of Cx43 to EGFP, in contrast, a in neurite and the functional of Cx were of Cx32 or Cx43 by with a in the of by the PC12 cells through Cx with or cells with and treated with a of was Cx43 PC12 cells with and following was not in were not neurite outgrowth is by Additional were and the Cx43 that hemichannels through either the of to not Connexin of PC12 cells with Cx32 or Cx43 resulted in cells that appropriately the Cx Both Cx32 and Cx43 were trafficked to the of cell-cell and functional gap junctions. of from PC12 cells treated with for several to of Cx32 or Cx43 in PC12 cells enhanced neurite outgrowth in cells with than or PC12 PC12 cells to the of that is not in PC12 However, by in the Cx cells by of that of the Cx is and to Cx hemichannels in an neurite following with Cx32 or Cx43 the of the was not likely the of providing the cells with a the in neurite the and cells to of and PC12 cells were to to adjacent cells in the or of NGF, the was following the of to and receptors in the plasma membrane of PC12 cells C.C. S. A. PubMed Scopus Google Scholar). PC12 cells treated with and the of S. A. PubMed Scopus Google Scholar). studies have shown that of several of the including protein is for neurite outgrowth and S. K. S. Nat. Cell Biol. 2005; PubMed Scopus Google Scholar, Cell. 1995; Full Text PDF PubMed Scopus Google Scholar, J. A. Neurosci. Lett. PubMed Scopus Google Scholar, J. K. M. J. Biol. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). Recently, that receptors cause Cx43 via of the protein kinase to enhanced cell-cell communication P. P. A. D.J. J. Neurosci. Res. 2005; PubMed Scopus Google Scholar). current study by that the of traditional gap channels as as Cx hemichannels suggesting that Cx may play an role in in the developing central nervous system. Connexin ATP in PC12 is evidence that Cx to signaling through the release of small molecules such as ATP or from hemichannels of membranes (2Goodenough D.A. Paul D.L. Nat. Rev. Mol. Cell. Biol. 2003; 4: 285-295Crossref PubMed Scopus (588) Google Scholar). results of the current study suggesting that enhanced neurite outgrowth in and cells was the consequence of a factor released into the media through Cx PC12 cells that expressed or in neurite outgrowth whether they expressed the Cx protein or results were including and factor most likely for the enhanced neurite outgrowth is studies have shown that functional hemichannels R. J. Cell Biol. PubMed Scopus Google Scholar, T.A. S. A. 1996; PubMed Scopus Google Scholar, A. C. J. Cell Biol. 1996; PubMed Scopus Google and that hemichannels formed by Cx43 in and cells release ATP Naus C.C. A.C. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). in have functional on Ca2+ For example, and Naus C.C. A.C. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google that the Cx hemichannel intercellular Ca2+ in cells not of the of Ca2+ suggesting that the Ca2+ were by the release of ATP through hemichannels Naus C.C. A.C. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). studies have shown that such as neurite outgrowth in PC12 cells and neurite with S. T. G. Neuroscience. PubMed Scopus Google Scholar, B. S. G. G. C. Neuroscience. 2001; PubMed Scopus Google Scholar). ATP as a for the enhanced neurite outgrowth in the current study several different were For example, PC12 cells were treated with ATP or either in the or of cells to with that in the Cx32 and Cx43 of to cells treated with ATP or resulted in neurite with was following the expression of Cx32 or Cx43 in PC12 cells treated with ATP to purinergic receptors and ATP and purinergic receptors have been shown to PC12 cell neurite outgrowth S. T. G. Neuroscience. PubMed Scopus Google Scholar, B. S. G. G. C. Neuroscience. 2001; PubMed Scopus Google Scholar). of purinergic receptors have been identified and and both are to be expressed by PC12 cells G. Int. Rev. 2004; PubMed Scopus Google Scholar). In the current study, of receptors or neurite outgrowth following as as ATP were found to be in the media of PC12 cells treated with cells and of ATP in the media with enhanced Cx hemichannel PC12 cells in media from cells enhanced neurite outgrowth that was by to the ATP in the Collectively, the in the current study the that enhanced in the Cx cells is by ATP release through Cx are a of signaling by that may be for the enhanced neurite outgrowth in the current For example, of ATP to the receptor to and S. J. Biol. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). to receptors on the the release of whereas protein kinase S. J. Biol. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). Both protein kinase and Ca2+ are by and the receptor and are for PC12 cell differentiation and neurite outgrowth J. 25: PubMed Scopus Google Scholar). and ATP likely on signaling to cause the enhanced neurite outgrowth in the current and are of development and although they may be expressed throughout the Both Cx32 and Cx43 are development and have been localized to developing neurons K. D.L. Parnavelas J.G. J. 2002; PubMed Scopus Google neurons of the D.S.Y. Unsicker K. Reuss B. Int. J. Dev. Neurosci. 2002; 20: 63-75Crossref PubMed Scopus (50) Google and neurons M. J. Neurosci. 1999; 19: PubMed Google Scholar). study by P. T. M. D. J. Neurosci. Res. PubMed Scopus Google that gap communication in cells resulted in cell and suggesting that gap junctions play an important functional role in central nervous Studies neuronal cell the that gap junctions are important in differentiation. For example, M. Naus C.C. 1999; PubMed Scopus Google the of gap on the differentiation of treated with gap with resulted in a in the of neurons that of with treated with results suggest that important or differentiation are cells or released through Cx Weissman T.A. Flint A.C. Kriegstein A.R. Neuron. 2004; Full Text Full Text PDF PubMed Scopus Google have that radial cells in the developing release ATP via Cx hemichannels that release from through a of the progenitor in the T.A. Flint A.C. Kriegstein A.R. Neuron. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). In the results of the current study suggest that Cx proteins may to neuronal differentiation in the developing central nervous through the release of molecules such as ATP in the and for the stages of the

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.