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Notch1 Signaling Influences V2 Interneuron and Motor Neuron Development in the Spinal Cord

2006; Karger Publishers; Volume: 28; Issue: 1-2 Linguagem: Inglês

10.1159/000090757

1421-9859

Xudong Yang, Taisuke Tomita, Mary Wines-Samuelson, Vassilios Beglopoulos, Malú G. Tansey, Raphael Kopan, Jie Shen,

Kruppel-like factors research

The Notch signaling pathway plays a variety of roles in cell fate decisions during development. Previous studies have shown that reduced Notch signaling results in premature differentiation of neural progenitor cells, while increased Notch activities promote apoptotic death of neural progenitor cells in the developing brain. Whether Notch signaling is involved in the specification of neuronal subtypes is unclear. Here we examine the role of Notch1 in the development of neuronal subtypes in the spinal cord using conditional knockout (cKO) mice lacking <i>Notch1</i> specifically in neural progenitor cells. Notch1 inactivation results in accelerated neuronal differentiation in the ventral spinal cord and gradual disappearance of the ventral central canal. These changes are accompanied by reduced expression of <i>Hes1 </i>and <i>Hes5</i> and increased expression of <i>Mash1 </i>and<i> Neurogenin 1</i> and <i>2.</i> Using markers (Nkx2.2, Nkx6.1, Olig2, Pax6 and Dbx1) for one or multiple progenitor cell types, we found reductions of all subtypes of progenitor cells in the ventral spinal cord of <i>Notch1</i> cKO mice. Similarly, using markers (Islet1/2, Lim3, Sim1, Chox10, En1 and Evx1/2) specific for motor neurons and distinct classes of interneurons, we found increases in the number of V0–2 interneurons in the ventral spinal cord of <i>Notch1</i> cKO mice. Specifically, the number of Lim3+/Chox10+ V2 interneurons is markedly increased while the number of Lim3+/Islet+motor neurons is decreased in the <i>Notch1</i> cKO spinal cord, suggesting that V2 interneurons are generated at the expense of motor neurons in the absence of Notch1. These results provide support for a role of Notch1 in neuronal subtype specification in the ventral spinal cord.