Li L, Schatteman G C, Oppenheim R W, Lei M, Bowen-Pope D F, Houenou L J
Department of Neurobiology and Anatomy, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
Brain Res Dev Brain Res. 1996 Oct 23;96(1-2):204-9. doi: 10.1016/0165-3806(96)00116-2.
The platelet-derived growth factor receptor alpha subunit (PDGFR alpha) is expressed by glial precursors, glial cells, and some peripheral neurons during normal rodent development. Its ligands are expressed ubiquitously in neurons, including sensory and motor neurons. Thus, neuronally secreted PDGF-A may play a paracrine role in the development of both glial cells and peripheral neurons. The Patch (Ph) mutation, which is a deletion of the PDGFR alpha, is a homozygous embryonic lethal mutation 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 mutation. However, whether and the extent to which motor and sensory neurons are affected by the mutation are not known. Here, we have examined the survival and/or morphological differentiation of spinal motor and sensory (dorsal root ganglion) neurons during the period of naturally occurring cell death, i.e., between E14 and E18, in control and Ph/Ph mice. The results show a 65-70% decrease in motor and sensory neuron numbers in Ph/Ph mice, compared to controls, at all stages examined. Furthermore, motoneurons in Ph/Ph mice were significantly smaller than those in controls. Because of the bidirectional nature of neuron-glial cell interactions, these results suggest that PDGFR alpha plays an important 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.
血小板衍生生长因子受体α亚基（PDGFRα）在正常啮齿动物发育过程中由神经胶质前体细胞、神经胶质细胞和一些外周神经元表达。其配体在神经元中广泛表达，包括感觉神经元和运动神经元。因此，神经元分泌的血小板衍生生长因子A（PDGF-A）可能在神经胶质细胞和外周神经元的发育中发挥旁分泌作用。Patch（Ph）突变是PDGFRα的缺失，是小鼠中的纯合胚胎致死突变。此前，已表明几种发育异常，包括许多器官结缔组织的缺陷、神经嵴细胞迁移异常以及嵴细胞非神经元衍生物的缺陷，都与Patch突变有关。然而，运动神经元和感觉神经元是否受该突变影响以及受影响的程度尚不清楚。在此，我们研究了对照小鼠和Ph/Ph小鼠在自然发生细胞死亡期间，即E14至E18期间，脊髓运动神经元和感觉（背根神经节）神经元的存活和/或形态分化。结果显示，在所有检测阶段，与对照小鼠相比，Ph/Ph小鼠的运动神经元和感觉神经元数量减少了65%-70%。此外，Ph/Ph小鼠的运动神经元明显小于对照小鼠的运动神经元。由于神经元与神经胶质细胞相互作用的双向性，这些结果表明PDGFRα在神经胶质细胞发育中起重要作用，从而间接在神经元细胞发育中起作用，或者，PDGF和PDGFRα通过自分泌/旁分泌机制直接参与外周神经元的存活和发育。
