Jagged2 Controls the generation of Motor Neuron and Oligodendrocyte progenitors in the ventral Spinal Cord

Elisa Marti (1) , Angeles Rabadan (1) , Jordi Cayuso (1) , Gwenvael Le Dreau (1) , Catarina Cruz (1) , Mercedes Barci (1) , Sebastian Pons (1) , James Briscoe (1)

1 Institut de Biologia Molecular de Barcelona

In the developing spinal cord, motor neurons and oligodendrocytes arise sequentially from a common pool of progenitors. However, the genetic network responsible for this neurogenesis to gliogenesis switch is largely unknown. A transcriptome analysis identified the Notch-ligand Jagged2 as a Shh-regulated factor transiently expressed in motor neuron progenitors (pMN). In vivo loss- and gain-of-function experiments show that Jagged2 schedules the differentiation of the pMN progenitors. At early developmental stages, Olig2 expressing pMN progenitors that enter the differentiation pathway exclusively generate motor neurons. At these times, the activation of the Notch pathway by Jagged2 maintains selected pMN progenitors in an undifferentiated state by two mechanisms; first inhibits MN generation by reducing Olig2 proteins levels, and second directly inhibits the premature generation of OLPs by maintaining high levels of Hes5. Later, extinction of Jagged2 from the pMN results in the loss of Hes5 expression, heralding the gliogenic phase of pMN progenitors. Strikingly, downregulation of Jagged2 in pMN progenitors is sufficient to promote the precocious generation of OLPs. Together these data provide evidence that Jagged2 is a key regulator of the the timely and ordered generation of two of the defining cell types in the spinal cord, motor neurons and OLPs.

Mots clés: Sonic hedgehog; NEUROGENESIS; motor neurons; OLIG2; HES5

Elisa Marti, Angeles Rabadan, Jordi Cayuso, Gwenvael Le Dreau, Catarina Cruz, et al.. Jagged2 Controls the generation of Motor Neuron and Oligodendrocyte progenitors in the ventral Spinal Cord. Cell Death and Differentiation, 2011, ⟨10.1038/cdd.2011.84⟩. ⟨hal-00655646⟩