eBriefing

Neural Stem Cells: From Development to Function

Neural Stem Cells
Reported by
Megan Stephan

Posted May 22, 2008

Overview

On March 20, 2008, the New York Academy of Sciences hosted a day-long symposium at which nine researchers in the neural stem cell field described their work in three major areas of research. The first three speakers, Cheng-Yu Lee of the University of Michigan, Weimin Zhong of Yale University, and Sally Temple of the New York Neural Stem Cell Institute, described their work on the signals and mechanisms that support symmetric versus asymmetric stem cell division.

The next three speakers, Oliver Hobert of Columbia University, Jeremy Dasen of New York University, and Stephen Noctor of the University of California at Davis, described work on the mechanisms by which the progeny of asymmetric divisions differentiate in specialized cells that form the components of the mature nervous system.

The last three speakers, René Hen of Columbia University, Tracey Shors of Rutgers University, and Fernando Nottebohm of the Rockefeller University, discussed their work on the functions of neurogenesis in adult organisms.

Web Sites

American Society for Neural Therapy and Repair
Professional society of basic and clinical neuroscientists using new technologies to study nervous system functions and establish new procedures for its repair.

Columbia University Medical Center Neural Stem Cell Program
Center committed to exploring the biology and therapeutic potential of stem cells for the treatment of neurological disorders.

International Society for Stem Cell Research
Independent, nonprofit organization promoting the exchange of information on stem cells.

National Human Neural Stem Cell Resource
Resource that provides neural stem cells to the research community.

New York Stem Cell Foundation
Nonprofit organization dedicated to furthering human embryonic stem cell research.

Stem Cell Basics
National Institutes of Health resource for information on stem cells and stem cell research.

Stem Cells and Parkinson's Disease
Article on stem cells and Parkinson's disease from the International Society for Stem Cell Research.


Publications

Cheng-Yu Lee

Lee CY, Andersen RO, Cabernard C, et al. 2006. Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev. 20: 3464-3474. Full Text

Lee CY, Wilkinson BD, Siegrist SE, et al. 2006. Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Developmental Cell 10: 441-449.

Lee CY, Robinson KJ, Doe CQ. 2006. Lgl, pins and aPKC regulate neuroblast self-renewal versus differentiation. Nature 439: 594-598.

Lee CY, Clough EA, Yellon P, et al. 2003. Genome-wide analyses of steroid- and radiation- triggered programmed cell death in Drosophila. Curr. Biol. 13: 350-357.

Rolls MM, Albertson R, Shih HP, et al. 2003. Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J. Cell Biol. 163: 1089-1098. Full Text

Lee CY, Simon CR, Woodard CT, et al. 2002. Genetic mechanism for the stage- and tissue-specific regulation of steroid triggered programmed cell death in Drosophila. Dev. Biol. 252: 138-148.

Weimin Zhong

Zhou Y, Atkins JB, Rompani SB, et al. 2007. The mammalian Golgi regulates numb signaling in asymmetric cell division by releasing ACBD3 during mitosis. Cell 129: 163-178.

Petersen PH, Tang H, Zou K, et al. 2006. The enigma of the numb-Notch relationship during mammalian embryogenesis. Dev. Neurosci. 28: 156-168.

Tang H, Rompani SB, Atkins JB, et al. 2005. Numb proteins specify asymmetric cell fates via an endocytosis- and proteasome-independent pathway. Mol. Cell Biol. 25: 2899-2909. Full Text

Petersen PH, Zou K, Krauss S, et al. 2004. Continuing role for mouse numb and numbl in maintaining progenitor cells during cortical neurogenesis. Nat. Neurosci. 7: 803-811.

Zhong W. 2003. Diversifying neural cells through order of birth and asymmetry of division. Neuron 37: 11-14.

Petersen PH, Zou K, Hwang JK, et al. 2002. Progenitor cell maintenance requires numb and numblike during mouse neurogenesis. Nature 419: 929-934.

Sally Temple

Fasano CA, Dimos JT, Ivanova NB, et al. 2007. shRNA knockdown of Bmi-1 reveals a critical role for p21-Rb pathway in NSC self-renewal during development. Cell Stem Cell 1: 87-99.

Lowry NA, Temple S. 2007. Making human neurons from stem cells after spinal cord injury. PLoS Med. 4: e48. Full Text

Shen Q, Wang Y, Dimos JT, et al. The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells. Nat. Neurosci. 9: 743-751.

Pumiglia K, Temple S. 2006. PEDF: bridging neurovascular interactions in the stem cell niche. Nat. Neurosci. 9: 299-300.

Capela A, Temple S. 2006. LeX is expressed by principle progenitor cells in the embryonic nervous system, is secreted into their environment and binds Wnt-1. Dev. Biol. 291: 300-313.

Abramova N, Charniga C, Goderie SK, et al. 2005. Stage-specific changes in gene expression in acutely isolated mouse CNS progenitor cells. Dev. Biol. 283: 269-281.

Shen Q, Goderie SK, Jin L, et al. 2004. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304: 1338-1340.

Temple S, Alvarez-Buylla A. 1999. Stem cells in the adult mammalian central nervous system. Curr. Opin. Neurobiol. 9: 135-141.

Oliver Hobert

Hobert O. 2008. Gene regulation by transcription factors and microRNAs. Science 319: 1785-1786.

Sarin S, O'Meara MM, Flowers EB, et al. 2007. Genetic screens for Caenorhabditis elegans mutants defective in left/right asymmetric neuronal fate specification. Genetics 176: 2109-2130. Full Text

Etchberger JF, Lorch A, Sleumer MC, et al. 2007. The molecular signature and cis-regulatory architecture of a C. elegans gustatory neuron. Genes Dev. 21: 1653-1674.

Hobert O. 2006. Architecture of a microRNA-controlled gene regulatory network that diversifies neuronal cell fates. Cold Spring Harb. Symp. Quant. Biol. 71: 181-188.

Poole RJ, Hobert O. 2006. Early embryonic programming of neuronal left/right asymmetry in C. elegans. Curr. Biol. 16: 2279-2292.

Bénard CY, Boyanov A, Hall DH, et al. 2006. DIG-1, a novel giant protein, non-autonomously mediates maintenance of nervous system architecture. Development 133: 3329-3340. Full Text

Ortiz CO, Etchberger JF, Posy SL, et al. 2006. Searching for neuronal left/right asymmetry: genomewide analysis of nematode receptor-type guanylyl cyclases. Genetics 173: 131-149. Full Text

Hobert O. 2005. Specification of the nervous system. WormBook 8: 1-19.

Jeremy Dasen

Dasen JS, Tice BC, Brenner-Morton S, et al. 2005. A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity. Cell 123: 477-491.

Dasen JS, Liu JP, Jessell TM. 2003. Motor neuron columnar fate imposed by sequential phases of Hox-c activity. Nature 425: 926-933.

Dasen JS, Barbera JP, Herman TS, et al. 2001. Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis. Genes Dev. 15: 3193-3207. Full Text

Dasen JS, Rosenfeld MG. 2001. Signaling and transcriptional mechanisms in pituitary development. Annu. Rev. Neurosci. 24: 327-55.

Rosenfeld MG, Briata P, Dasen J, et al. 2000. Multistep signaling and transcriptional requirements for pituitary organogenesis in vivo. Recent Prog. Horm. Res. 55: 1-13; discussion 13-14.

Dasen JS, Rosenfeld MG. 1999. Signaling mechanisms in pituitary morphogenesis and cell fate determination. Curr. Opin. Cell Biol. 11: 669-677.

Stephen Noctor

Noctor SC, Martínez-Cerdeño V, Kriegstein AR. 2008. Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J. Comp. Neurol. 508: 28-44.

Noctor SC, Martínez-Cerdeño V, Kriegstein AR. 2007. Contribution of intermediate progenitor cells to cortical histogenesis. Arch. Neurol. 64: 639-642.

Martínez-Cerdeño V, Noctor SC, Kriegstein AR. 2006. Estradiol stimulates progenitor cell division in the ventricular and subventricular zones of the embryonic neocortex. Eur. J. Neurosci. 24: 3475-3488.

Martínez-Cerdeño V, Noctor SC, Kriegstein AR. 2006. The role of intermediate progenitor cells in the evolutionary expansion of the cerebral cortex. Cereb. Cortex 16 Suppl 1: i152-il61.

Kriegstein AR, Noctor SC. 2004. Patterns of neuronal migration in the embryonic cortex. Trends Neurosci. 27: 392-399.

Noctor SC, Martínez-Cerdeño V, Ivic L, et al. 2004. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat. Neurosci. 7: 136-144.

Weissman T, Noctor SC, Clinton BK, et al. 2003. Neurogenic radial glial cells in reptile, rodent and human: from mitosis to migration. Cereb. Cortex. 13: 550-559. Full Text

René Hen

Wang JW, David DJ, Monckton JE, et al. 2008. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J. Neurosci. 28: 1374-1384.

Sahay A, Drew MR, Hen R. 2007. Dentate gyrus neurogenesis and depression. Prog. Brain Res. 163: 697-722.

Sahay A, Hen R. 2007. Adult hippocampal neurogenesis in depression. Nat. Neurosci. 10: 1110-1115.

Drew MR, Hen R. 2007. Adult hippocampal neurogenesis as target for the treatment of depression. CNS Neurol. Disord. Drug Targets 6: 205-218.

Pereira AC, Huddleston DE, Brickman AM, et al. 2007. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc. Natl. Acad. Sci. USA 104: 5638-5643. Full Text

Saxe MD, Malleret G, Vronskaya S, et al. 2007. Paradoxical influence of hippocampal neurogenesis on working memory. Proc. Natl. Acad. Sci. USA 104: 4642-4646. Full Text

Sanders AC, Hussain AJ, Hen R, et al. 2007. Chronic blockade or constitutive deletion of the serotonin transporter reduces operant responding for food reward. Neuropsychopharmacology 32: 2321-2329.

David DJ, Klemenhagen KC, Holick KA, et al. 2007. Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis. J. Pharmacol. Exp. Ther. 321: 237-248. Full Text

Tracey Shors

Shors TJ, Mathew J, Edgecomb C, et al. 2007. Neurogenesis is mediated by learned helplessness in males but not females. Biological Psychiatry 62: 487-95.

Bangasser DA, Shors TJ. 2007. The hippocampus is necessary for enhancements and impairments of learning following stress. Nat. Neurosci. 10: 1401-1403.

Sisti HM, Glass AL, Shors TJ. 2007. Neurogenesis and the spacing effect: learning over time enhances memory and the survival of new neurons. Learn. Mem. 14: 368-375. Full Text

Dalla C, Bangasser DA, Edgecomb C, et al. 2007. Neurogenesis and learning: acquisition and asymptotic performance predict how many new cells survive in the hippocampus. Neurobiol. Learn. Mem. 88: 143-148.

Leuner B, Waddell J, Gould E, et al. 2006. Temporal discontiguity is neither necessary nor sufficient for learning-induced effects on adult neurogenesis. J. Neurosci. 26: 13437-13442. Full Text

Bangasser DA, Waxler DE, Santollo J, et al. 2006. Trace conditioning and the hippocampus: the importance of contiguity. J. Neurosci. 26: 8702-8706. Full Text

Leuner B, Gould E, Shors TJ. 2006. Is there a link between adult neurogenesis and learning? Hippocampus 16: 216-224.

Shors TJ. 2006. Stressful experience and learning across the lifespan. Annu. Rev. Psychol. 57: 55-85.

Shors TJ. 2006. Significant life events and the shape of memories to come: a hypothesis. Neurobiol. Learn. Mem. 85: 103-115.

Leuner B, Mendolia-Loffredo S, Kozorovitskiy Y, et al. 2004. Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J. Neurosci. 24: 7477-7481. Full Text

Shors TJ, Miesegeas G, Beylin A, et al. 2001. Neurogenesis in the adult is involved in the formation of trace memories. Nature 410: 372-376.

Fernando Nottebohm

Liu WC, Nottebohm F. 2007. A learning program that ensures prompt and versatile vocal imitation. Proc. Natl. Acad. Sci. USA 104: 20398-20403.

Agate RJ, Hertel M, Nottebohm F. 2007. FnTm2, a novel brain-specific transcript, is dynamically expressed in the song learning circuit of the zebra finch. J. Comp. Neurol. 504: 127-148.

Barkan S, Ayali A, Nottebohm F, et al. 2007. Neuronal recruitment in adult zebra finch brain during a reproductive cycle. Dev. Neurobiol. 67: 687-701.

Wilbrecht L, Williams H, Gangadhar N, et al. 2006. High levels of new neuron addition persist when the sensitive period for song learning is experimentally prolonged. J. Neurosci. 26: 9135-9141. Full Text

Barnea A, Mishal A, Nottebohm F. 2006. Social and spatial changes induce multiple survival regimes for new neurons in two regions of the adult brain: An anatomical representation of time? Behav. Brain Res. 167: 63-74.

Liu WC, Nottebohm F. 2005. Variable rate of singing and variable song duration are associated with high immediate early gene expression in two anterior forebrain song nuclei. Proc. Natl. Acad. Sci. USA 102: 10724-9. Full Text

Gardner TJ, Naef F, Nottebohm F. 2005. Freedom and rules: the acquisition and reprogramming of a bird's learned song. Science 308: 1046-1049.

Nottebohm F. 2005. The neural basis of birdsong. PLoS Biol. 3: e164. Full Text

Speakers

Cheng-Yu Lee, PhD

University of Michigan
e-mail | web site | publications

Cheng-Yu Lee is a professor in the Life Sciences Institute at the University of Michigan. His research focuses on the molecular mechanisms by which genes in Drosophila regulate self-renewal vs. differentiation in fly neuroblasts. His goal is to identify signaling pathways expressed in insect and vertebrate neural stem cells, and their role in birth defects, regenerative medicine, and cancer biology. Lee completed his graduate studies at the University of Maryland and postgraduate work at the University of Oregon. In 2006 he was the recipient of a Career Award in Biomedical Research from the Burroughs Wellcome Foundation.

Weimin Zhong, PhD

Yale University
e-mail | web site | publications

Weimin Zhong is an associate professor of molecular, cellular, and developmental biology at Yale University. He uses neurogenesis in mice as a model system to study how neural stem (progenitor) cells are maintained and how neuronal diversity is generated in the mammalian nervous system. In particular, his team is probing the behavior of stem cells by changing their patterns of division, examining how cell fates are assigned to maintain tissue homeostasis, and using embryonic stem cells to probe human developmental mechanisms. Zhong completed his PhD at the Rockefeller University.

Sally Temple, PhD

Albany Medical College
e-mail | web site | publications

Sally Temple is a professor at the Center for Neuropharmacology & Neuroscience at Albany Medical College and a member of the New York Neural Stem Cell Institute. She studies how embryonic neural progenitor cells generate various cell types of the adult central nervous system. Known for her work in designing systems for culturing neural progenitor cells and for designing innovative approaches to tracking how precursors divide and renew, she is currently studying how neural stem cells interact with their environment, particularly with the vascular system. Temple completed her PhD at University College London, and completed postdoctoral fellowships at Columbia University and the University of Miami.

Oliver Hobert, PhD

Columbia University
e-mail | web site | publications

Oliver Hobert is associate professor of biochemistry and molecular biophysics at Columbia University. His lab studies the developmental aspects of neural circuit generation as well as later aspects of maintenance and modification of neural circuits. Using C. elegans as a model system, he is working in particular to understand mechanisms that determine neuronal cell fate and axon patterning.

Jeremy Dasen, PhD

New York University
e-mail | web site | publications

Jeremy Dasen is an assistant professor at the Sackler Institute of New York University School of Medicine. Using genetic manipulations in chick and mouse models, his lab is exploring the relationships between the identity of neural cells and how they move to develop neural circuits. He has been particularly interested in a set of transcription factors in the Hox family and is investigating their role in the molecular interactions that control circuit assembly. Dasen completed his graduate studies in 1999 at the University of California, San Diego.

Stephen C. Noctor, PhD

University of California at Davis
e-mail | web site | publications

Stephen Noctor is an assistant professor in residence in the Department of Psychiatry and Behavioral Sciences at the University of California at Davis. He studies development of cortical structures in the central nervous system with particular attention to the factors that control proliferation of the precursor cells that produce cortical neurons and glia, and how cortical cells migrate over long distances to reach their appropriate position in the developing brain. Noctor completed his graduate training at the Uniformed Services University of the Health Sciences in 1998.

René Hen, PhD

Columbia University
e-mail | web site | publications

René Hen is a professor of pharmacology in Columbia University's Department of Psychiatry and its Center for Neurobiology and Behavior. He studies the relationship between serotonin and behavior, with a particular interest in the role of serotonin in anxiety and mood disorders. In recent years he has been investigating the hypothesis that hippocampal neurogenesis is a requirement in order for antidepressant medications. Hen received his PhD in 1985 from the Université Louis Pasteur. His awards and honors include a 2003 Distinguished Investigator Grant from the National Alliance for Research on Schizophrenia and Depression, a 2000 Doctor Harold and Golden Lamport Award for Excellence in Basic Science Research, and a Bristol-Myers Squibb Neuroscience Award.

Tracey J. Shors, PhD

Rutgers University
e-mail | web site | publications

Tracey Shors is a professor in the Department of Psychology and Center for Collaborative Neuroscience at Rutgers University. Shors joined the Rutgers University faculty in 1997 from Princeton University after graduate and postdoctoral studies at the University of Southern California. Her research goals are to understand how the production of new neurons into adulthood relates to how memories are formed and stored in the brain. Her research efforts also address sex differences in the brain and how males and females differ in their ability to learn and respond to stressful experiences.

Fernando Nottebohm, PhD

The Rockefeller University
e-mail | web site | publications

Fernando Nottebohm is Dorothea L. Leonhardt Distinguished Professor at the Rockefeller University and director of the Rockefeller Field Research Center for Ethology and Ecology, where he studies bird behavior and brain function in a natural setting. Nottebohm is a pioneer in study of the neural control of birdsong and played an important role in proving that the vertebrate brain continues to produce new neurons into adulthood. He is a member of the National Academy of Sciences, and a fellow of the American Association for the Advancement of Science and the American Academy of Arts and Sciences.


Megan Stephan

Megan Stephan studied transporters and ion channels at Yale University for nearly two decades before giving up the pipettor for the pen. She specializes in covering research at the interface between biology, chemistry and physics. Her work has appeared in The Scientist and Yale Medicine. Stephan holds a PhD in biology from Boston University.