The Japanese Society of Developmental Biologists
Develop. Growth Differ. (2011) 53, 225–235
doi: 10.1111/j.1440-169X.2010.01226.x
Review Article
Programmed cell death during postnatal development of the rodent nervous system Woon Ryoung Kim and Woong Sun* Department of Anatomy, Korea University College of Medicine, Brain Korea 21, Anam-Dong, Sungbuk-Gu, Seoul 136-705, Korea
During development, elimination of excess cells through programmed cell death (PCD) is essential for the establishment and maintenance of the nervous system. In many brain regions, development and major histogenesis continue beyond postnatal stages, and therefore, signs of neurogenesis and PCD are frequently observed in these postnatal brain regions. Furthermore, some brain regions maintain neurogenic potential throughout life, and continuous genesis and PCD play critical roles in sculpting these adult neural circuits. Although similar regulatory mechanisms that control PCD during development appear to also control PCD in the adult brain, adult-generated neurons must integrate into mature neural circuits for their survival. This novel requirement appears to result in unique features of PCD in the adult brain. In this article, we summarize recent findings related to PCD in the early postnatal and adult brain in rodents. Key words: adult neurogenesis, cell death, dentate gyrus, olfactory bulb, postnatal development.
Introduction During embryonic development, many neural cells undergo programmed cell death (PCD). This active elimination process is believed to be required for proper establishment and maintenance of the nervous system (Buss et al. 2006). PCD of neural cells is found during most stages of development including proliferation, migration, axonal guidance, and synaptogenesis. It has been proposed that PCD has at least three major functions during embryonic development (Buss et al. 2006): (i) limiting the proliferating pool size during neurogenesis; (ii) correcting errors and removing developmentally transient structures; and (iii) quantitatively matching neurons with efferent targets and afferent inputs for optimal neuronal connections during synaptogenesis. The time-course of neuronal development is highly diverse depending on the neuronal population, and accordingly the time-course of PCD in each *Author to whom all correspondence should be addressed. Email:
[email protected] Received 1 September 2010; revised 28 September 2010; accepted 29 September 2010. ª 2011 The Authors Journal compilation ª 2011 Japanese Society of Developmental Biologists
neural population is different. Because major developmental processes continue postnatally in some brain regions, it is not surprising that PCD occurs in these areas of the postnatal brain (Buss et al. 2006; Oppenheim 1991). For example, neurogenesis of granuletype neurons in the cerebellum, dentate gyrus (DG), and olfactory bulb (OB) is active until 2–3 weeks after birth, and PCD of neural progenitors occurs in these brain regions. Synaptogenesis is also active in many early postnatal brain regions including the cerebral cortex, midbrain, cerebellum, and retina. Therefore, PCD of post-mitotic neurons during synaptogenesis is also abundant in these brain regions. It has recently become clear that at least some adult brain regions maintain neural stem cells that spontaneously produce new neurons in adulthood. Adult neurogenesis is evident in most species including rodents (Altman 1963; Privat & Leblond 1972), primates (Gould et al. 1998), and humans (Eriksson et al. 1998; Bernier et al. 2000; Curtis et al. 2007). Similar to the situation during embryonic and early postnatal development, substantial numbers of newly generated neurons in adult brain are eliminated by PCD (Biebl et al. 2000; Petreanu & Alvarez-Buylla 2002; Dayer et al. 2003; Sun et al. 2004; Ninkovic et al. 2007; Snyder et al. 2009). Because neurons born in the adult brain must
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integrate and synaptically connect with other mature neurons for their survival, adult neurogenesis and PCD continuously change neural circuits.
PCD of neurons in the early postnatal brain (
