Specification, multipotency and plasticity during embryonic & adult neurogenesis


Nora Abrous, Arturo Alvarez-Buylla, Paola Arlotta, Yves-Alain Barde, James Briscoe, Elisabeth Dupin, Carol Erickson, Patrik Ernfors, Magdalena Götz, Wieland B. Huttner, Jane Johnson, Ryoichiro Kageyama, Chaya Kalcheim (organisateur), Juergen Knoblich, Arnold Kriegstein, Nicole Le Douarin, Pierre-Marie Lledo (organisateur), Adi Mizrahi, Amar Sahay, Lukas Sommer, Song Hongjun


Specification, multipotency and plasticity during embryonic & adult neurogenesis
by Chaya Kalcheim and Pierre-Marie Lledo
24 – 29 October 2011

In october 24-29, 2011, a group of 21 scientists gathered at the Fondation des Treilles to hold a meeting entitled “Specification, multipotency and plasticity during embryonic and adult neurogenesis”. This meeting was organized by Chaya Kalcheim (Hebrew University of Jerusalem) and Pierre-Marie Lledo (Pasteur Institute).
The field of stem cells and more specifically, neural stem cells, has attracted much attention during the past years. Neural stem cells (NSCs) are the self-renewing, multipotent cells that generate the main phenotypes of the peripheral and central nervous systems. In the embryo, a hierarchy of developmental restrictions generates differentiated cell types from multipotent progenitors. However, the state of specification of progenitor cells at different stages and embryonic sites is not well defined. Elucidation of the above is essential for understanding the mechanisms leading to fate restriction in normal development.
Stem cells are not unique to embryos. In 1992, Reynolds and Weiss were the first to isolate neural progenitors and stem cells from the striatum, including the subventricular zone of adult mouse brain tissue. Since then, neural progenitor and stem cells have been isolated from various areas of the adult spinal cord and brain, and from various species including human. It is hypothesized that neurogenesis in the adult brain originates from NSCs. Yet, the origin, identity and functional properties of NSCs in the adult brain remain to be defined.
The workshop focused on the latest advances in the mechanisms responsible for proliferation, maintenance, differentiation and function of neural stem cell/progenitors. Using an array of model organisms (avians, mice, drosophila, humans, cultured cells), diverse systems were addressed: from Neural Crest progenitors to their peripheral neural vs melanocytic derivatives; several central neuronal types like cortical, hippocampal and olfactory bulb neurons and glia, etc.
The main topics that were discussed included the following:

FROM STEM CELL TO TERMINAL NEUROGENIC DIVISIONS (Huttner, Knoblich, Kriegstein, Kageyama, Song)
During brain development, neurons arise from neural stem and progenitor cells, which initially proliferate by symmetric divisions and later switch to both asymmetric and symmetric neurogenic divisions. Multiple types of progenitors exist with different characteristics and modes of division. To control the number, type, and final location of neurons, the transition from proliferative to neurogenic cell divisions requires a complex network of regulation so that neural specification, cell-cycle exit, cell differentiation and neuronal migration can all occur in concert. These concepts were discussed for bothembryonic and adult processes.

FATE DECISIONS DURING NEURAL DEVELOPMENT (Le Douarin, Kalcheim, Erickson, Ernfors, Briscoe, Sommer, Johnson, Dupin, Barde).
Neuronal fate determination is an essential stage in both embryonic and adult neurogenesis. Embryonic microenvironments within the neural tube/nascent brain, in peripheral ganglia, and neurogenic niches in the adult, provide instructional signals that control proliferation, differentiation and survival of the stem cell pool to ensure that neurogenesis continues throughout life. Current knowledge regarding the mechanisms that control the undifferentiated state and fate determination of embryonic peripheral and central neurons as well as of adult neural stem cells in the hippocampus and olfactory bulb were discussed.

Neural progenitors often migrate through stereotypic pathways until homing to their final destinations. The neural crest offers an excellent example for such a paradigm. Is there a deterministic relationship between the state of specification of a progenitor and the routes of migration it follows?. Alternatively, are these two independently-regulated processes, yet merely coordinated in time to ensure successful morphogenesis? Furthermore, the session dealt with questions regarding the timing of fate decisions and the extent to which these depend upon environmental cues.

REGULATION OF ADULT NEUROGENESIS (Arlotta, Sahay, Abrous, Lledo, Song, Alvarez-Buylla, Götz, Mizrahi)
The molecular pathways important for adult neurogenesis, including transcriptional and epigenetic regulatory factors, and signaling mechanisms during physiological and pathological contexts were discussed.

FUNCTIONAL INTEGRATION OF ADULT-GENERATED NEURONS (Abrous, Song, Sahay, Lledo, Arlotta, Götz, Alvarez-Buylla, Mizrahi)
Newborn neurons in the adult circuits differentiate and integrate within the existing neuronal circuitry. This topic addressed how the impact of adult-born neurons in neuronal networks is dictated by the extent that newborn neurons participate as part of the network and how their intrinsic properties compare with those of existing neurons generated during development.

FUNCTIONAL SIGNIFICANCE OF ADULT NEUROGENESIS (Abrous, Song, Sahay, Lledo, Arlotta, Götz, Alvarez-Buylla, Mizrahi).
Newly formed neurons incorporate into functional networks suggesting important roles for adult neurogenesis in some cognitive functions. This session presented the current evidence regarding the functional roles that newborn neurons play in the adult brain.

NEUROLOGICAL DISORDERS AND REPAIR (Abrous, Song, Sahay, Lledo, Götz, Alvarez-Buylla, Mizrahi).
Recent studies have shown that a wide variety of stimuli, including seizures, stress, stroke, and chronic antidepressant treatment, can profoundly affect adult neurogenesis. Moreover, neurodegenerative disease states are often associated with diminished neurogenesis. This session addressed whether failure of a normal reparative process, i.e., adult neurogenesis, contributes to the development of disease, and/or whether enhancing neurogenesis could be used as a therapeutic strategy in some of these disorders.

For further details, click here to read the abstracts summarizing each presentation.

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