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

Summary: 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
thattwoV1IN-relatedtranscriptionfactorgenesplayinRenshawcelldevelopment.Pax6( pairedboxgene6)isnecessaryforanearlystep
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
Recent studies have identified five early classes of neurons in the


Source: Alvarez, Francisco J. - Department of Neuroscience, Cell Biology, and Physiology, Wright State University


Collections: Biology and Medicine