An <i>in vivo</i> analysis of Schwann cell programmed cell death in embryonic mice: the role of axons, glial growth factor, and the pro‐apoptotic gene <i>Bax</i>

Winseck, Adam K.; Oppenheim, Ronald W.

doi:10.1111/j.1460-9568.2006.05107.x

Cited by 21 publications

(13 citation statements)

References 63 publications

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“…4k,l). Apoptotic cell death2,23 (measured by TdT-mediated dUTP nick end (TUNEL) labeling) was unaffected in E17 nerves of the three Notch mutants (Supplementary Fig. 3 online).…”

Section: Resultsmentioning

confidence: 99%

Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity

et al. 2009

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Notch signaling is central to vertebrate development, and analysis of Notch has provided important insights into pathogenetic mechanisms in the CNS and many other tissues. However, surprisingly little is known about the role of Notch in the development and pathology of Schwann cells and peripheral nerves. Using transgenic mice and cell cultures, we found that Notch has complex and extensive regulatory functions in Schwann cells. Notch promoted the generation of Schwann cells from Schwann cell precursors and regulated the size of the Schwann cell pool by controlling proliferation. Notch inhibited myelination, establishing that myelination is subject to negative transcriptional regulation that opposes forward drives such as Krox20. Notably, in the adult, Notch dysregulation resulted in demyelination; this finding identifies a signaling pathway that induces myelin breakdown in vivo. These findings are relevant for understanding the molecular mechanisms that control Schwann cell plasticity and underlie nerve pathology, including demyelinating neuropathies and tumorigenesis.

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“…4k,l). Apoptotic cell death2,23 (measured by TdT-mediated dUTP nick end (TUNEL) labeling) was unaffected in E17 nerves of the three Notch mutants (Supplementary Fig. 3 online).…”

Section: Resultsmentioning

confidence: 99%

Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity

et al. 2009

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“…However, we consider it unlikely that the regression of axons in our mutant embryos reflects a loss of Schwann cells. Presumptive Schwann cells [32] are present in the Blad homozygotes and, although the role of glia in the Blad phenotype has not been examined, the effects of Wld s on axon survival is intrinsic to axons vs. glia. Following in vitro injury to neurites from Wld s expressing neurons cultured in the absence of glia (Schwann cells), the transected neurites exhibit delayed Wallerian degeneration [33], [34].…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide Mononucleotide Adenylyltransferase 2 (Nmnat2) Regulates Axon Integrity in the Mouse Embryo

et al. 2012

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Using transposon-mediated gene-trap mutagenesis, we have generated a novel mouse mutant termed Blad (Bloated Bladder). Homozygous mutant mice die perinatally showing a greatly distended bladder, underdeveloped diaphragm and a reduction in total skeletal muscle mass. Wild type and heterozygote mice appear normal. Using PCR, we identified a transposon insertion site in the first intron of Nmnat2 (Nicotinamide mononucleotide adenyltransferase 2). Nmnat2 is expressed predominantly in the brain and nervous system and has been linked to the survival of axons. Expression of this gene is undetectable in Nmnat2blad/blad mutants. Examination of the brains of E18.5 Nmnat2blad/blad mutant embryos did not reveal any obvious morphological changes. In contrast, E18.5 Nmnat2blad/blad homozygotes showed an approximate 60% reduction of spinal motoneurons in the lumbar region and a more than 80% reduction in the sensory neurons of the dorsal root ganglion (DRG). In addition, facial motoneuron numbers were severely reduced, and there was virtually a complete absence of axons in the hind limb. Our observations suggest that during embryogenesis, Nmnat2 plays an important role in axonal growth or maintenance. It appears that in the absence of Nmnat2, major target organs and tissues (e.g., muscle) are not functionally innervated resulting in perinatal lethality. In addition, neither Nmnat1 nor 3 can compensate for the loss of Nmnat2. Whilst there have been recent suggestions that Nmnat2 may be an endogenous modulator of axon integrity, this work represents the first in vivo study demonstrating that Nmnat2 is involved in axon development or survival in a mammal.

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“…, 2003). Furthermore, because the Bax‐KO SCZ contains more axons from rescued neurons that could secondarily support the survival of myelinating oligodendrocytes, oligodendrocyte PCD may also be reduced by a non‐cell‐autonomous mechanism (Winseck & Oppenheim, 2006).…”

Section: Discussionmentioning

confidence: 99%

Evidence for the spontaneous production but massive programmed cell death of new neurons in the subcallosal zone of the postnatal mouse brain

Kim¹,

Chun²,

Kim³

et al. 2011

European Journal of Neuroscience

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In the last 10 years, many studies have reported that neural stem/progenitor cells spontaneously produce new neurons in a subset of adult brain regions, including the hippocampus, olfactory bulb (OB), cerebral cortex, substantia nigra, hypothalamus, white matter and amygdala in several mammalian species. Although adult neurogenesis in the hippocampus and OB has been clearly documented, its occurrence in other brain regions is controversial. In the present study, we identified a marked accumulation of new neurons in the subcallosal zone (SCZ) of Bax-knockout mice in which programmed cell death (PCD) of adult-generated hippocampal and OB neurons has been shown to be completely prevented. By contrast, in the SCZ of wild-type (WT) mice, only a few immature (but no mature) newly generated neurons were observed, suggesting that virtually all postnatally generated immature neurons in the SCZ were eliminated by Bax-dependent PCD. Treatment of 2-month-old WT mice with a caspase inhibitor, or with the neurotrophic factor brain-derived neurotrophic factor, promoted the survival of adult-generated neurons, suggesting that it is the absence of sufficient neurotrophic signaling in WT SCZ that triggers the Bax-dependent, apoptotic PCD of newly generated SCZ neurons. Furthermore, following focal traumatic brain injury to the posterior brain, SCZ neurogenesis in WT mice was increased, and a subset of these newly generated neurons migrated toward the injury site. These data indicate that the adult SCZ maintains a neurogenic potential that could contribute to recovery in the brain in response to the injury-induced upregulation of neurotrophic signaling.

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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

Cited by 21 publications

References 63 publications

Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity

Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity

Nicotinamide Mononucleotide Adenylyltransferase 2 (Nmnat2) Regulates Axon Integrity in the Mouse Embryo

Evidence for the spontaneous production but massive programmed cell death of new neurons in the subcallosal zone of the postnatal mouse brain

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