ALTERED DEVELOPMENT OF SPINAL-CORD IN THE MOUSE MUTANT (PATCH) LACKING THE PDGF RECEPTOR ALPHA-SUBUNIT GENE

The platelet-derived growth factor receptor alpha subunit (PDGFR alpha ) is expressed by glial precursors, glial cells, and some peripheral n eurons during normal rodent development. Its ligands are expressed ubi quitously in neurons, including sensory and motor neurons. Thus, neuro nally secreted PDGF-A may play a paracrine role in the development of both glial cells and peripheral neurons. The Patch (Ph) mutation, whic h is a deletion of the PDGFR alpha, is a homozygous embryonic lethal m utation in the mouse. Previously, several developmental abnormalities, including deficiencies in connective tissues in many organs, aberrant neural crest cell migration, and defects in non-neuronal derivatives of crest cells, have been shown to be associated with the Patch mutati on. Hen-ever, whether and the extent to which motor and sensory neuron s are affected by the mutation are not known. Here, we have examined t he survival and/or morphological differentiation of spinal motor and s ensory (dorsal root ganglion) neurons during the period of naturally o ccurring cell death, i.e., between E14 and E18, in control and Ph/Ph m ice. The results show a 65-70% decrease in motor and sensory neuron nu mbers in Ph/Ph mice, compared to controls, at all stages examined, Fur thermore, motoneurons in Ph/Ph mice were significantly smaller than th ose in controls. Because of the bidirectional nature of neuron-glial c ell interactions, these results suggest that PDGFR alpha plays an impo rtant role in glial cell development and, thus, indirectly in neuronal cell development or, alternatively, that PDGF and the PDGFR alpha are directly involved in peripheral neuron survival and development by an autocrine/paracrine mechanism.