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Neuroscience Graduate Program at UCSF

Faculty - Arturo Alvarez-Buylla, Ph.D.

Birth and Migration of New Neurons


Research Description

Our laboratory studies the mechanisms of adult neurogenesis and neuronal replacement.  Contrary to the dogma held for over a century, some populations of neurons continue to be produced in juvenile and adult brains.  Basic mechanisms of neural development can be studied in a fully assembled brain, providing key insights into the nature of neural stem cells, mechanisms of neuronal migration, and neural maturation.

Our goals are to understand:

1) How young neurons are generated.

2) How young neurons migrate long distances.

3) How young neurons differentiate and contribute to brain function and possibly brain tumors.

4) Whether similar processes can be used for brain repair is also studied in the lab.

We have identified the neural stem cells (NSCs), intermediate progenitors cells, and lineages for adult neurogenesis in the adult mammalian ventricular-subventricular zone (V-SVZ).  This is the most extensive germinal niche in the adult mammalian brain.  These NSCs integrate information within the niche and also receive axonal input from local and distant sources.  NSCs in the V-SVZ generate large numbers of new neurons that migrate long distances through the complex matrix of the postnatal brain. New neurons then differentiate into local-circuit neurons that become incorporated into the olfactory bulb.  We are studying the properties of adult NSCs, their embryonic origins, and their mode of division.

We are also studying the V-SVZ in the human brain.  We found that in infants the V-SVZ contains many migrating young neurons.  Interestingly, in addition to the migration to the olfactory bulb (OB) in young children, new neurons derived from the V-SVZ migrate towards cortex.  We are investigating: 1) The regions of cortex where these new young neurons migrate to; 2) During which period of human postnatal development they contribute new neurons to cortical circuits; and 3) What types of neurons they generate.
  
Replacement of local circuit neurons (interneurons) is a promising new approach for brain repair; however, we have found that V-SVZ neurogenesis is highly tailored for the production of olfactory bulb neurons.  We are investigating the potential of young neurons derived from the embryonic medial ganglionic eminence (MGE) for brain repair.  The MGE is a major source of inhibitory local circuit neurons for the cerebral cortex.  Unlike, neurons derived from the adult V-SVZ, young MGE neurons can migrate and functional integrate into the adult brain outside of the olfactory bulb.  In collaboration with other laboratories at UCSF, we have found that these cells can induce a new period of plasticity in the visual cortex, can ameliorate seizures in epileptic mice, and can reduce pain thresholds in spinal cord circuits.  We are studying how these cells integrate into adult cortex and which populations of interneurons are responsible for the above therapeutic effects.

The laboratory uses mostly in vivo approaches.  We take advantage of the collaborative environment at UCSF to use multiple levels of analysis to understand the mechanisms of adult neuronal replacement at the molecular, cellular, circuit, and behavior levels.

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Publications

Link to Publications via PubMed

Fuentealba LC, Rompani SB, Parraguez JI, Obernier K, Romero R, Cepko CL, Alvarez-Buylla A. Embryonic Origin of Postnatal Neural Stem Cells. Cell [Internet]. 2015;161(7):1644–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26091041 PMID: 26091041

Tate MC, Lindquist RA, Nguyen T, Sanai N, Barkovich AJ, Huang EJ, Rowitch DH, Alvarez-Buylla A. Postnatal growth of the human pons: A morphometric and immunohistochemical analysis. The Journal of comparative neurology [Internet]. 2014 Oct 10 [cited 2014 Oct 23]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/25307966 PMID: 25307966

Lim DA, Alvarez-Buylla A. Adult neural stem cells stake their ground. Trends in neurosciences [Internet]. 2014 Oct [cited 2014 Oct 9];37(10):563–571. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25223700 PMID: 25223700

Tong CK, Han Y-G, Shah JK, Obernier K, Guinto CD, Alvarez-Buylla A. Primary cilia are required in a unique subpopulation of neural progenitors. Proceedings of the National Academy of Sciences of the United States of America [Internet]. 2014 Aug 11 [cited 2014 Aug 21];1–6. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.1321425111 PMID: 25114218

Ohata S, Nakatani J, Herranz-Pérez V, Cheng J, Belinson H, Inubushi T, Snider WD, García-Verdugo JM, Wynshaw-Boris A, Alvarez-Buylla A. Loss of Dishevelleds Disrupts Planar Polarity in Ependymal Motile Cilia and Results in Hydrocephalus. Neuron [Internet]. Elsevier Inc.; 2014 Aug 6 [cited 2014 Aug 11];83(3):558–571. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25043421 PMID: 25043421

Obernier K, Tong CK, Alvarez-Buylla A. Restricted nature of adult neural stem cells: Re-evaluation of their potential for brain repair. Frontiers in Neuroscience. 2014. PMID: 24987325\

Southwell DG, Nicholas CR, Basbaum AI, Stryker MP, Kriegstein AR, Rubenstein JL, Alvarez-Buylla A. Interneurons from embryonic development to cell-based therapy. Science (New York, NY) [Internet]. 2014 Apr 11 [cited 2014 Apr 18];344(6180):1240622. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24723614 PMID: 24723614

Tong CK, Chen J, Cebrián-Silla A, Mirzadeh Z, Obernier K, Guinto CD, Tecott LH, García-Verdugo JM, Kriegstein A, Alvarez-Buylla A. Axonal control of the adult neural stem cell niche. Cell stem cell [Internet]. 2014 Apr 3 [cited 2014 Apr 10];14(4):500–11. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24561083 PMID: 24561083

Merkle FT, Fuentealba LC, Sanders TA, Magno L, Kessaris N, Alvarez-Buylla A. Adult neural stem cells in distinct microdomains generate previously unknown interneuron types. Nature neuroscience [Internet]. 2014 Feb [cited 2014 Feb 3];17(2):207–14. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24362763 PMID: 24362763

Ponti G, Obernier K, Alvarez-Buylla A. Lineage progression from stem cells to new neurons in the adult brain ventricular-subventricular zone. Cell cycle (Georgetown, Tex) [Internet]. 2013 Jun 1 [cited 2014 Feb 3];12(11):1649–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23673324 PMID: 23673324

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Arturo Alvarez-Buylla, Ph.D.



Email

abuylla@stemcell.ucsf.edu

Phone

415-514-2348

Office Address

Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research
UCSF Box 0525
35 Medical Center Way, RMB-1036              
San Francisco, CA 94143-0525  

Other Websites

Lab Website