Caspase Activity Is Involved in, but Is Dispensable for, Early Motoneuron Death in the Chick Embryo Cervical Spinal Cord

Yaginuma, Hiroyuki; Shiraiwa, Nobuko; Shimada, Takako; Nishiyama, Keiji; Hong, Jin-Hyuk; Wang, Siwei; Momoi, Takashi; Uchiyama, Yasuo; Oppenheim, Ronald W.

doi:10.1006/mcne.2001.1009

Cited by 43 publications

(48 citation statements)

References 64 publications

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“…Lim-3) may be involved in the process death is accompanied by caspase-3 activation and can be prevented by Bcl-2, suggesting that both early and later MN death may involve a similar execution pathway. 15,[34][35][36] However, in the present study, we found that Bax overexpression does not enhance this early cervical MN death, even though hBax appears to be activated in dying MNs which exhibit caspase-3 activation. These results suggest that the lack of an enhancement of PCD in cervical MNs by Bax overexpression is not likely due to a distinct execution pathway that is independent of Bax.…”

Section: Discussioncontrasting

confidence: 83%

“…15,23,34 Primary antibodies used in this study were the anti-Islet-1/2 (clone 4D5, Developmental Studies Hybridoma Bank, DSHB), anti-Lim-3 (clone 67.4E12, DSHB), antiviral p19 GAG protein (clone AMV-3C2, DSHB), antiactivated caspase-3 (clone C92-605, Pharmingen), and anti-Bax (clone 4F11, MBL). We tested three distinct antibodies for hBax from either Santa Cruz (polyclonal antibody, N-20), MBL (monoclonal antibody, 4F11), or Pharmingen (polyclonal antibody).…”

Section: Chicken Embryo Virus Infection and In Ovo Electroporationmentioning

confidence: 99%

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Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo

et al. 2005

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Bax is a proapoptotic protein that is required for programmed cell death (PCD) of many neuronal populations. Here we show that, during an early period of retinal PCD and in naturally occurring sensory and motor neuron (MN) death in the spinal cord, Bax delivery results in enhanced death of these neural populations. In contrast, Bax overexpression fails to enhance an early phase of MN death that occurs in the cervical spinal cord, although overexpressed Bax appears to be activated in dying MNs. Bax overexpression does not also affect the survival of immature neurons prior to the PCD period. Taken together, these data provide the first in vivo evidence suggesting that Bax appears to act selectively as an executioner only in neurons undergoing PCD. Furthermore, although Bax appears to mediate the execution pathway for PCD, the effect of Bax overexpression on susceptibility to death differs between different neuronal populations.

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Section: Discussioncontrasting

confidence: 83%

Section: Chicken Embryo Virus Infection and In Ovo Electroporationmentioning

confidence: 99%

Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo

et al. 2005

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“…Serial transverse sections (6 -8 m) were obtained from embryonic, postnatal, and adult mice, and stained with either hematoxylin-eosin (H&E) or thionin, and neurons were counted blind in every 5th (brain) or 10th (spinal cord, SCG) section using a method previously validated against a stereological optical disector method (Clarke and Oppenheim, 1995) (R. W. Oppenheim, unpublished data). As previously described in chick embryos after treatment with caspase inhibitors (Yaginuma et al, 2001), and in mouse embryos with genetic deletion of caspase-3 or caspase-9 (Oppenheim et al, 2001a; present study), the morphology of degenerating neurons in these embryos differs from the typical type 1 apoptotic cell death observed in control/WT embryos (see Results). For this reason, the analysis of degenerating cells in the Apaf-1 mutants also includes these atypical presumptive dying neurons.…”

Section: Methodssupporting

confidence: 76%

“…However, a considerable amount of PCD in the developing nervous system also involves more mature differentiating postmitotic neurons that are establishing synaptic connections, and this aspect of neuronal PCD was not examined in the abovementioned studies. We previously reported that the extent of neuronal PCD during this later phase is unaffected by the genetic deletion of either caspase-3 or caspase-9 (Oppenheim et al, 2001a) and the PCD of postmitotic motor neurons (MNs) in the chick embryo has also been shown to be unaffected after the pharmacological inhibition of caspases (Yaginuma et al, 2001). In the present study, we examined PCD in several populations of target-dependent neurons in Apaf-1 knock-out (KO) mice, and contrary to a previous report (Honarpour et al, 2001a), we find that PCD occurs to the same extent as in wild-type (WT) control animals.…”

Section: Introductionmentioning

confidence: 99%

Developing Postmitotic Mammalian NeuronsIn VivoLacking Apaf-1 Undergo Programmed Cell Death by a Caspase-Independent, Nonapoptotic Pathway Involving Autophagy

Oppenheim¹,

Blomgren²,

Ethell³

et al. 2008

J. Neurosci.

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Previous studies have shown that caspases and Apaf-1 are required for the normal programmed cell death (PCD) in vivo of immature postmitotic neurons and mitotically active neuronal precursor cells. In contrast, caspase activity is not necessary for the normal PCD of more mature postmitotic neurons that are establishing synaptic connections. Although normally these cells use caspases for PCD, in the absence of caspase activity these neurons undergo a distinct nonapoptotic type of degeneration. We examined the survival of these more mature postmitotic neuronal populations in mice in which Apaf-1 has been genetically deleted and find that they exhibit quantitatively normal PCD of developing postmitotic neurons. We next characterized the morphological mode of PCD in these mice and show that the neurons degenerate by a caspase-independent, nonapoptotic pathway that involves autophagy. However, autophagy does not appear to be involved in the normal PCD of postmitotic neurons in which caspases and Apaf-1 are present and functional because quantitatively normal neuronal PCD occurred in the absence of a key gene required for autophagy (ATG7). Finally, we examined the possible role of another caspase-independent type of neuronal PCD involving the apoptosis-inducing factor (AIF). Mice deficient in AIF also exhibit quantitatively normal PCD of postmitotic neurons after caspase inhibition. Together, these data indicate that, when key components of the type 1 apoptotic pathway (i.e., caspases and Apaf-1) are perturbed in vivo, developing postmitotic neurons nonetheless undergo quantitatively normal PCD by a caspase-independent pathway involving autophagy and not requiring AIF.

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“…36 Similar findings were made for motoneurons in chick embryos upon caspase inhibition. 37 The differential behavior of forebrain and nonforebrain neurons in the mutant mice discussed above indicates that distinct cell types (within the same species and the same organ) can house distinct potential cell death mechanisms. Similarly, in some tissues of adult C. elegans necrotic cell death can occur, 38 suggesting that the nonredundancy of apoptotic developmental cell death in this organism, as analyzed by Horvitz et al, 39 is due to tissue-specific expression of only one of several possible cell death mechanisms.…”

Section: Inhibition/replacement Of Cell Death Typesmentioning

confidence: 99%

Redundant cell death mechanisms as relics and backups

Golstein

Kroemer

2005

Cell Death Differ

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Here we review recent observations indicating the existence of redundant cell death mechanisms. We speculate that this redundancy reflects a particular evolutionary history for cellular demise. Autophagic or apoptotic elements might have been added to a primordial death mechanism, initially improving cell dismantling and later acquiring the ability to act themselves as death effectors. The resulting redundancy of cell death mechanisms has pathophysiological implications.

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Caspase Activity Is Involved in, but Is Dispensable for, Early Motoneuron Death in the Chick Embryo Cervical Spinal Cord

Cited by 43 publications

References 64 publications

Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo

Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo

Developing Postmitotic Mammalian NeuronsIn VivoLacking Apaf-1 Undergo Programmed Cell Death by a Caspase-Independent, Nonapoptotic Pathway Involving Autophagy

Redundant cell death mechanisms as relics and backups

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