2013
DOI: 10.1016/j.devcel.2013.11.015
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Local Apoptosis Modulates Early Mammalian Brain Development through the Elimination of Morphogen-Producing Cells

Abstract: Apoptotic cells are observed in the early developing brain. Apoptosis deficiency is proposed to cause brain overgrowth, but here we show that brain malformations in apoptosis-deficient mutants are due to insufficient brain ventricle expansion as a result of uncompleted cranial neural tube closure. Apoptosis eliminates Fgf8-expressing cells in the anterior neural ridge (ANR), which acts as an organizing center of the forebrain by producing FGF8 morphogen. Deficiency of apoptosis leads to the accumulation of und… Show more

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Cited by 92 publications
(93 citation statements)
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References 71 publications
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“…2Ai). This pattern of apoptosis in the developing brain is consistent with previous reports of a low background of apoptosis involved in proper brain development (Chan et al, 2002, Nonomura et al, 2013, Rakic and Zecevic, 2000. Embryos injected with Kv1.5 (hyperpolarizing) mRNA into the dorsal two cells at four-cell stage (ii,iii) …”
Section: Both Local and Distant V Mem Signals Regulate Apoptosis In Tsupporting
confidence: 79%
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“…2Ai). This pattern of apoptosis in the developing brain is consistent with previous reports of a low background of apoptosis involved in proper brain development (Chan et al, 2002, Nonomura et al, 2013, Rakic and Zecevic, 2000. Embryos injected with Kv1.5 (hyperpolarizing) mRNA into the dorsal two cells at four-cell stage (ii,iii) …”
Section: Both Local and Distant V Mem Signals Regulate Apoptosis In Tsupporting
confidence: 79%
“…Apoptosis in these cells around the notochord and the developing brain could disrupt such critical inductive interactions by either eliminating signal producing cells or signal receiving cells. Such secondary effect of apoptosis on inductive interactions during brain development have previously been documented (Nonomura et al, 2013). Hence, this apoptosis in the regions around notochord and developing brain may also be responsible for the observed defects in brain morphology upon perturbation of bioelectric signals.…”
Section: Local and Distant V Mem Patterns Regulate Apoptosis And Prolmentioning
confidence: 92%
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“…1 When cell death is inhibited, tissues can become enlarged and disorganized, resulting in decreased organismal viability. 2 The developing nervous system is particularly susceptible to altered levels of programmed cell death, which may be important for both robustness and flexibility in the nervous system development. 3,4 Understanding the pathways that regulate developmental death will provide insight not only into the developmental program but also into the pathophysiology of nervous system diseases such as neurodegeneration.…”
mentioning
confidence: 99%
“…Specifically, Apaf1 or Caspase-3 mediated apoptosis at the site of fusion of the neural folds during the midbrain and hindbrain's neural tube closure was found not to be essential for completion of neural tube closure (Massa et al, 2009). Equally intriguing was the recent finding by Nonomura and colleagues showing that Apaf1 or Caspase-9-mediated apoptosis occurring specifically in the developing brain's anterior neural ridge (ANR) area was responsible for the regulation of brain development's early phases (Nonomura et al, 2013). Indeed, according to Nonomura and colleagues, initial causes of the brain abnormalities observed in Apaf1 -/-and Caspase-9 -/-mice were due to insufficient brain ventricle expansion occurring at early developmental stages, these then leading to uncomplete closure of cranial neural tube (Nonomura et al, 2013).…”
Section: Apaf1 In Neurodevelopmentmentioning
confidence: 93%