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The Journal of Neuroscience, March 1, 1998, 18(5):1753-1762
Changes in the Properties of Gap Junctions during Neuronal
Differentiation of Hippocampal Progenitor Cells
Renato
Rozental1, 2, 6,
Mildred
Morales1,
Mark F.
Mehler1, 3, 4,
Marcia
Urban1,
Marion
Kremer7,
Rolf
Dermietzel7,
John A.
Kessler1, 3, and
David C.
Spray1, 5, 6
Departments of 1 Neuroscience,
2 Anesthesiology, 3 Neurology,
4 Psychiatry, and 5 Medicine, Albert Einstein
College of Medicine, Bronx, New York, 10461, 6 Department
of Internal Medicine and IPTESP, Federal University of Goi ,
Goiânia 74000, Brazil, and 7 Ruhr University Bochum,
D-44780 Bochum, Germany
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  ,
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.
Key words:
connexins; electrotonic coupling; development; cytokines; Cx33; Cx40; Cx43
Copyright © 1998 Society for Neuroscience 0270-6474/98/1851753-10$05.00/0
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