Programmed Cell Death Meeting Review in the Developing Nervous System
1996
Several of the earliest experiments underlying our un-derstanding of cell death were aimed at defining theOne of the most striking features of the rapidly devel-trophic dependence of a given cell on interactions withoping field of thestudy of programmed cell death(PCD)its cellular partners. Although the first of these werehas been the relativeuniversality of many of the mecha-performed over 90 years ago (Oppenheim; P. G. H.nisms uncovered and, indeed, of the very existence ofClarke, University of Lausanne), experimental ablationmolecular apoptotic programs. The possibility of usingof cells or tissues in vivo continues to provide muchinformation from one system to understand death innew information,especiallysinceclassical microsurgeryother, very different cells will undoubtedly continue totechniques (Oppenheim)can nowbe combined withthebe a major impetus for discovery. However, the finalmore cell-specific methods of pharmacological (J. Cal-purposeanddetailedimplications of PCDmayvarycon-dero`, University of Lleida; Clarke) or genetic (K. White,siderably from system to system. Careful analysis ofMassachusetts General Hospital) cell removal. How-the cell death process in each population is thereforerequired if the normal biology of apoptosis is to be un- ever, biological systems do not react passively to suchderstood in depth. insults, and this can lead to problems of interpretation.Thisis particularlytrue inthe developing nervous sys- A niceexample of this isprovided byone of theclassicaltem, where many different cell types undergo PCD at ablation models (Oppenheim). Following limb-bud re-different stages. Indeed, early work by V. Hamburger moval in the earlychick embryo, there is massive motorandR.Levi-Montalcinionnaturallyoccurringand lesion- neuron loss in the spinal cord, but only a 50% loss ofinduced cell death of developing neurons laid the foun- sensory neurons, suggesting that the latter may survivedations for the subsequent explosion of the study of independently of their target tissue. In fact, this turnsapoptosis in general. Eventhey, however, may not have out to be due at least in part to an adaptive reaction ofsuspectedatthetimetheextenttowhichsuchconcepts the sensory neuronsthemselves. In theabsence of limb,would permeate different aspects of developmental they project ectopically to the tail bud, where they pre-neurobiology. Many striking illustrations of this were sumably find alternative trophic support. When the tailprovided by presentations at a recent workshop orga- bud is removed as well, then sensory neuron numbersnized at the Juan March Institute in Madrid by R. W. are further reduced (Oppenheim).Oppenheim (Wake Forest University), E. M. Johnson Even where trophic support is important, it may not(Washington University), and J. X. Comella (University be theonlyfactorinvolvedinregulating neuronnumbersof Lleida) on“Programmed CellDeath in the Developing during the period of naturally occurring cell death. OnlyNervous System.” The results presented demonstrate male zebra finches sing, and this correlates with sex-that not only do different neural cells die for different related differences in several nuclei implicated in songreasonsand bydifferent mechanisms,butthat ina given behaviorthat resultfrom increased PCDinfemales (E.J.cell, theprecise mechanism of PCD may vary as a func- Nordeen, University of Rochester). Section of afferenttion of the death-inducing stimulus. pathways from the lateral magnocellular nucleus andI have organized this meeting review along the lines the high vocal center leads in both sexes to increasedof the temporal sequence of events that take place in PCD in the robust nucleus of the anterior neostriatuma cell undergoing PCD. The first phase, often referred (RA; Burek et al., 1995). However, the sex-related differ-to as the “triggering” of cell death, groups together a ences in neuron numbers are retained, suggesting thatseries ofinfluencesthat mayinstigatethedeathprocess hormonal influences play an important role in commit-invivo, but whichare less irrevocableor immediatethan ting some neurons to PCD. It is possible that thesethe firing of a pistol. I have therefore referred to these influences may be mediated by sex differences in glio-collectively as “life on the edge.” A cell in this situation genesis in the RA nucleus that are apparent before thehassubsequentlytotakethedecisiontodieortosurvive onsetofsexuallydimorphicPCD(NordeenandNordeen,(“Will she, won’t he?”), and then to initiate the complex 1996).seriesof molecularandmorphologicalchangesinvolved Identification of the trophic factors that mediate thein cell death and disposal of the remains (“Getting on survival-promoting effects of one cell population on an-with the job”). The distinction between these three other has been the focus of intensive effort for manyphases is not as clear in many vertebrate neural cells years now. As a result, not only are the physiologicallyas in the nematode, in particular because a given ef- relevant factors now quite numerous, but they turn outfector may act at more than one stage in the process. to belong to a number of different gene families (neuro-However, they continue to provide a useful framework trophins, cytokines, transforming growth factorbs, etc.)for comparingresultsfrom differentsystems.In summa- that wascompletely unsuspected10years ago(Hender-rizing the many new results presented during the three son,1996).Nevertheless,therewas ageneralconsensus
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
13
References
0
Citations
NaN
KQI