Morrison-Graham K, Schatteman G C, Bork T, Bowen-Pope D F, Weston J A
Institute of Neuroscience, University of Oregon, Eugene 97403.
Development. 1992 May;115(1):133-42. doi: 10.1242/dev.115.1.133.
The Patch (Ph) mutation in mice is a deletion of the gene encoding the platelet-derived growth factor receptor alpha subunit (PDGFR alpha). Patch is a recessive lethal recognized in heterozygotes by its effect on the pattern of neural crest-derived pigment cells, and in homozygous mutant embryos by visible defects in craniofacial structures. Since both pigment cells and craniofacial structures are derived from the neural crest, we have examined the differentiation of other crest cell-derived structures in Ph/Ph mutants to assess which crest cell populations are adversely affected by this mutation. Defects were found in many structures populated by non-neuronal derivatives of cranial crest cells including the thymus, the outflow tract of the heart, cornea, and teeth. In contrast, crest-derived neurons in both the head and trunk appeared normal. The expression pattern of PDGFR alpha mRNA was determined in normal embryos and was compared with the defects present in Ph/Ph embryos. PDGFR alpha mRNA was expressed at high levels in the non-neuronal derivatives of the cranial neural crest but was not detected in the crest cell neuronal derivatives. These results suggest that functional PDGF alpha is required for the normal development of many non-neuronal crest-derived structures but not for the development of crest-derived neuronal structures. Abnormal development of the non-neuronal crest cells in Ph/Ph embryos was also correlated with an increase in the diameter of the proteoglycan-containing granules within the crest cell migratory spaces. This change in matrix structure was observed both before and after crest cells had entered these spaces. Taken together, these observations suggest that functional PDGFR alpha can affect crest development both directly, by acting as a cell growth and/or survival stimulus for populations of non-neurogenic crest cells, and indirectly, by affecting the structure of the matrix environment through which such cells move.
小鼠中的Patch（Ph）突变是编码血小板衍生生长因子受体α亚基（PDGFRα）的基因缺失。Patch是一种隐性致死突变，杂合子中可通过其对神经嵴衍生色素细胞模式的影响而识别，纯合突变胚胎中则可通过颅面结构的明显缺陷识别。由于色素细胞和颅面结构均源自神经嵴，我们研究了Ph/Ph突变体中其他嵴细胞衍生结构的分化，以评估哪些嵴细胞群体受到该突变的不利影响。在许多由颅嵴细胞的非神经元衍生物构成的结构中发现了缺陷，包括胸腺、心脏流出道、角膜和牙齿。相比之下，头部和躯干中源自嵴的神经元看起来正常。测定了正常胚胎中PDGFRα mRNA的表达模式，并与Ph/Ph胚胎中存在的缺陷进行了比较。PDGFRα mRNA在颅神经嵴的非神经元衍生物中高水平表达，但在嵴细胞神经元衍生物中未检测到。这些结果表明，功能性PDGFα是许多非神经元嵴衍生结构正常发育所必需的，但不是嵴衍生神经元结构发育所必需的。Ph/Ph胚胎中非神经元嵴细胞的异常发育也与嵴细胞迁移空间内含蛋白聚糖颗粒直径的增加相关。在嵴细胞进入这些空间之前和之后均观察到了基质结构的这种变化。综上所述，这些观察结果表明，功能性PDGFRα可直接影响嵴的发育，作为非神经源性嵴细胞群体的细胞生长和/或存活刺激因子，也可间接影响，通过影响此类细胞移动所通过的基质环境的结构。
