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An in vivo analysis of Schwann cell programmed cell death in embryonic mice: the role of axons, glial growth factor, and the pro‐apoptotic gene Bax
Author(s) -
Winseck Adam K.,
Oppenheim Ronald W.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.05107.x
Subject(s) - schwann cell , programmed cell death , biology , microbiology and biotechnology , embryonic stem cell , apoptosis , neuroglia , axon , neuroscience , immunology , central nervous system , genetics , gene
Building upon previous in vitro studies, the present investigation involves an in vivo examination of Schwann cell programmed cell death (PCD) and development in the brachial spinal ventral roots of embryonic mice. The period of Schwann cell PCD was found to occur between embryonic days (E) 11.5 and 18.5, which is in close coincidence with the PCD period of associated brachial motoneurons (E13.5–E18.5). Additionally, Schwann cells exhibited a peak in proliferation at E11.5, and differentiation from the precursor to the immature Schwann cell stage between E12.5 and E14.5. Axon‐mediated Schwann cell survival was demonstrated in vivo by excitotoxic elimination of motoneurons and their axons, via NMDA treatment in utero . This treatment increased apoptotic Schwann cell death within degenerating ventral roots. Conversely, in utero co‐treatment of glial growth factor (GGF) with NMDA resulted in decreased Schwann cell death, a finding which supports previous reports of the promotion of Schwann cell survival by GGF. Analysis of mice lacking Bax, a pro‐apoptotic Bcl‐2 protein, revealed that Schwann cell PCD occurred independently of Bax. However, owing to the lack of motoneuron PCD in Bax‐knockout mice, and the corresponding increase in the number of ventral root axons, a decrease in Schwann cell PCD was observed during the normal period of motoneuron PCD. In conclusion, our findings regarding the regulation of Schwann cell development in vivo are consistent with the conclusions from in vitro studies, including a dependency on axons for survival and proliferation signals, timing of differentiation, and a dependency on GGF.