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First published online January 10, 2008
doi: 10.1242/10.1242/jcs.023143

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Pyramidal neuron polarity axis is defined at the bipolar stage

Froylan Calderon de Anda^1,*, Annette Gärtner^2,*,, Li-Huei Tsai^1,3 and Carlos G. Dotti^2,

¹ Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 46, Room 4235A, Cambridge, MA 02139, USA
² VIB Department of Molecular and Developmental Genetics and Department of Human Genetics, Catholic University of Leuven, 3000 Leuven, Herestraat 49, Belgium
³ Howard Hughes Medical Institute, 77 Massachusetts Avenue, Building 46, Room 4235A, Cambridge, MA 02139, USA

Authors for correspondence (e-mails: Annette.Gaertner{at}med.kuleuven.be; carlos.dotti{at}med.kuleuven.be)

Accepted 29 October 2007

In situ observations of the development of hippocampal and cortical neurons indicate that final axon-dendrite identity is defined at the time of generation of the first two, oppositely positioned, neurites. Quite differently, in vitro studies demonstrated that axonal fate is defined by the stochastic selection of one of the multiple minor neurites for fast outgrowth. By analyzing the fate of all neurites, starting at the time of emergence from the cell body, we demonstrate that polarity is defined at the bipolar stage, with one of the two first-appearing neurites acquiring axonal fate, irrespective of how many other neurites later form. The first two neurites have, as in vivo, the highest growth potential, as cutting the axon results in the growth of a new axon from the neurite at the opposite pole, and cutting this induces regrowth from the first. This temporal and spatial hierarchical definition of polarized growth, together with the bipolar organization of microtubule dynamics and membrane transport preceding it, is consistent with polarity being initiated by an intrinsic program. In this scenario, molecules required for axon specification would act at one of the first two neurites and extrinsic cues will be required for final commitment of polarity.

Key words: Neuronal polarity, Axon, Bipolar growth

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