Nature Neuroscience 9, 770 - 778 (2006)
Published online: 21 May 2006; | doi:10.1038/nn1706
Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneuronsRumiko Mizuguchi1, 4, Sonja Kriks1, 4, Ralf Cordes3, Achim Gossler3, Qiufu Ma2
& Martyn Goulding11
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. 2
Department of Cancer Biology, Dana Farber Cancer Institute, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA. 3
Institute for Molecular Biology, Medizinische Hochschule Hannover, Carl Neuberg Strasse 1, Hannover, Germany. 4
These authors contributed equally to the work.
Correspondence should be addressed to Martyn Goulding goulding@salk.edu Sensory information from the periphery is integrated and transduced by excitatory and inhibitory interneurons in the dorsal spinal cord. Recent studies have identified a number of postmitotic factors that control the generation of these sensory interneurons. We show that Gsh1/2 and Ascl1 (Mash1), which are expressed in sensory interneuron progenitors, control the choice between excitatory and inhibitory cell fates in the developing mouse spinal cord. During the early phase of neurogenesis, Gsh1/2 and Ascl1 coordinately regulate the expression of Tlx3, which is a critical postmitotic determinant for dorsal glutamatergic sensory interneurons. However, at later developmental times, Ascl1 controls the expression of Ptf1a in dILA progenitors to promote inhibitory neuron differentiation while at the same time upregulating Notch signaling to ensure the proper generation of dILB excitatory neurons. We propose that this switch in Ascl1 function enables the cogeneration of inhibitory and excitatory sensory interneurons from a common pool of dorsal progenitors.
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