| First Author | Gauthier AS | Year | 2007 |
| Journal | Neuron | Volume | 54 |
| Issue | 2 | Pages | 245-62 |
| PubMed ID | 17442246 | Mgi Jnum | J:132094 |
| Mgi Id | MGI:3775129 | Doi | 10.1016/j.neuron.2007.03.027 |
| Citation | Gauthier AS, et al. (2007) Control of CNS cell-fate decisions by SHP-2 and its dysregulation in Noonan syndrome. Neuron 54(2):245-62 |
| abstractText | Within the developing mammalian CNS, growth factors direct multipotent precursors to generate neurons versus glia, a process that if perturbed might lead to neural dysfunction. In this regard, genetic mutations resulting in constitutive activation of the protein tyrosine phosphatase SHP-2 cause Noonan Syndrome (NS), which is associated with learning disabilities and mental retardation. Here, we demonstrate that genetic knockdown of SHP-2 in cultured cortical precursors or in the embryonic cortex inhibited basal neurogenesis and caused enhanced and precocious astrocyte formation. Conversely, expression of an NS SHP-2 mutant promoted neurogenesis and inhibited astrogenesis. Neural cell-fate decisions were similarly perturbed in a mouse knockin model that phenocopies human NS. Thus, SHP-2 instructs precursors to make neurons and not astrocytes during the neurogenic period, and perturbations in the relative ratios of these two cell types upon constitutive SHP-2 activation may contribute to the cognitive impairments in NS patients. |
