Changes in the properties of gap junctions during neuronal differentiation of hippocampal progenitor cells

Renato Rozental, Mildred Morales, Mark F. Mehler, Marcia Urban, Marion Kremer, Rolf Dermietzel, John A. Kessler, David C. Spray

Research output: Contribution to journalArticle

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Abstract

The cellular mechanisms that regulate progenitor cell lineage elaboration and maturation during embryonic development of the mammalian brain are poorly understood. Conditionally immortalized mouse hippocampal multipotent progenitor cells (MK31 cells) were found to be strongly coupled by gap junctions comprising connexin 43 (Cx43) during early neuronal ontogeny; the presence of this Cx type was confirmed by electrophysiological, molecular biological, and immunocytochemical assays. However, as progenitor cells underwent intermediate stages of neuronal differentiation under the influence of interleukin 7 (IL-7) alone or terminal differentiation after composite exposure to basic fibroblast growth factor, IL-7, and transforming growth factor α, coupling strength and the level of Cx43 expression declined. An additional population of junctional channels with distinct properties was detected at an intermediate stage of neuronal differentiation. Reverse transcription-PCR assays detected mRNA encoding Cx40 in IL-7-treated cells and Cx33 after both treatment conditions. Because functional channels in exogenous expression systems are not formed by pairing Cx40 with Cx43 or by pairing Cx33 with itself or additional connexins, these experimental observations raise the possibility that the progressive loss of coupling during differentiation of neural progenitor cells may involve downregulation of Cx43 coupled with potentiation of expression of Cx33 and Cx40. Furthermore, continued expression of Cx43 in differentiating neuroblasts could mediate intercellular communication between neuronal precursor cells and astrocytes by direct signaling via homotypic gap junction channels.

Original languageEnglish (US)
Pages (from-to)1753-1762
Number of pages10
JournalJournal of Neuroscience
Volume18
Issue number5
StatePublished - Mar 1 1998

Fingerprint

Electrical Synapses
Connexin 43
Stem Cells
Interleukin-7
Gap Junctions
Fibroblast Growth Factor 7
Connexins
Transforming Growth Factors
Fibroblast Growth Factor 2
Cell Lineage
Astrocytes
Biological Assay
Reverse Transcription
Embryonic Development
Down-Regulation
Polymerase Chain Reaction
Messenger RNA
Brain
Population

Keywords

  • Connexins
  • Cx33
  • Cx40
  • Cx43
  • Cytokines
  • Development
  • Electrotonic coupling

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Changes in the properties of gap junctions during neuronal differentiation of hippocampal progenitor cells. / Rozental, Renato; Morales, Mildred; Mehler, Mark F.; Urban, Marcia; Kremer, Marion; Dermietzel, Rolf; Kessler, John A.; Spray, David C.

In: Journal of Neuroscience, Vol. 18, No. 5, 01.03.1998, p. 1753-1762.

Research output: Contribution to journalArticle

Rozental, R, Morales, M, Mehler, MF, Urban, M, Kremer, M, Dermietzel, R, Kessler, JA & Spray, DC 1998, 'Changes in the properties of gap junctions during neuronal differentiation of hippocampal progenitor cells', Journal of Neuroscience, vol. 18, no. 5, pp. 1753-1762.
Rozental, Renato ; Morales, Mildred ; Mehler, Mark F. ; Urban, Marcia ; Kremer, Marion ; Dermietzel, Rolf ; Kessler, John A. ; Spray, David C. / Changes in the properties of gap junctions during neuronal differentiation of hippocampal progenitor cells. In: Journal of Neuroscience. 1998 ; Vol. 18, No. 5. pp. 1753-1762.
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