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The Journal of Neuroscience, February 4, 2004, 24(5):1255-1264; doi:10.1523/JNEUROSCI.3187-03.2004

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 Previous Article

Development/Plasticity/Repair
Pax6 and Engrailed 1 Regulate Two Distinct Aspects of Renshaw Cell Development

Tamar Sapir,1 Eric J. Geiman,1,2 Zhi Wang,3 Tomoko Velasquez,1 Sachiko Mitsui,4 Yoshihiro Yoshihara,4 Eric Frank,3 Francisco J. Alvarez,2 and Martyn Goulding1

1Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, 2Department of Anatomy, Wright State University, Dayton, Ohio 45435, 3Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, and 4Laboratory for Neurobiology of Synapse, The Institute of Physical and Chemical Research (RIKEN) Brain Science Institute, Wako, Saitama 351-0198, Japan

Many of the interneuron cell types present in the adult spinal cord contribute to the circuits that control locomotion and posture. Little is known, however, about the embryonic origin of these cell types or the molecular mechanisms that control their differentiation. Here we provide evidence that V1 interneurons (INs), an embryonic class of interneurons that transiently express the En1 transcription factor, differentiate as local circuit inhibitory interneurons and form synapses with motor neurons. Furthermore, we show that a subset of V1 INs differentiates as Renshaw cells, the interneuronal cell type that mediates recurrent inhibition of motor neurons. We analyze the role that two V1 IN-related transcription factor genes play in Renshaw cell development. Pax6 (paired box gene 6) is necessary for an early step in Renshaw cell development, whereas Engrailed 1 (En1), which is genetically downstream of Pax6, regulates the formation of inhibitory synapses between Renshaw cells and motor neurons. Together, these results show that Pax6 and En1 have essential roles in establishing the recurrent inhibitory circuit between motor neurons and Renshaw cells.

Key words: spinal cord development; Renshaw cells; recurrent inhibition; En1; Pax6; V1 interneurons


Received July 4, 2003; revised December 9, 2003; accepted December 12, 2003.




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