Manova K, Bachvarova R F, Huang E J, Sanchez S, Pronovost S M, Velazquez E, McGuire B, Besmer P
Molecular Biology Department, Sloan Kettering Institute, New York, New York 10021.
J Neurosci. 1992 Dec;12(12):4663-76. doi: 10.1523/JNEUROSCI.12-12-04663.1992.
The c-kit receptor and its cognate ligand, KL, are encoded at the white spotting locus (W) and the steel locus (Sl) of the mouse, respectively. Sl and W mutations affect the same cellular targets in melanogenesis, gametogenesis and hematopoiesis during embryonic development and in adult life. c-kit is expressed in cellular targets of W and Sl mutations, whereas KL is expressed in the microenvironment of these targets. c-kit and KL, however, are also expressed in tissues and cell types that are not targets of W and Sl mutations, including the brain. The cerebellum contains a small number of neural cell types whose developmental origins, pathways of migration, and synaptic contacts are known. We have investigated the patterns of expression of the c-kit and KL RNA and protein products in postnatal cerebellar development of the mouse. In the adult cerebellum, c-kit RNA and protein expression was evident in basket, stellate, and Golgi neurons. Most strikingly, the c-kit protein is expressed in the basket cell axons that form "basket" and "pinceau" structures entwining the Purkinje cell soma and the initial segment of the Purkinje cell axon. KL RNA expression was found in Purkinje cells, and the KL protein was detected in Purkinje cell bodies and dendrites. Soluble KL protein was also present in c-kit-expressing basket, stellate, and Golgi cells, presumably as a result of internalization of ligand-receptor complexes. During postnatal development, c-kit and KL RNA and protein expression in Golgi and Purkinje neurons, respectively, was evident by day 0 and persisted subsequently. c-kit expression in basket and stellate cells was detected from their time of birth, starting at day 4. These results suggest a role for the c-kit receptor system in postnatal development of the cerebellum.
c-kit受体及其同源配体KL分别由小鼠的白斑位点(W)和Steel位点(Sl)编码。Sl和W突变在胚胎发育及成年期影响黑素生成、配子发生和造血过程中的相同细胞靶点。c-kit在W和Sl突变的细胞靶点中表达,而KL在这些靶点的微环境中表达。然而,c-kit和KL也在非W和Sl突变靶点的组织和细胞类型中表达,包括脑。小脑包含少数已知其发育起源、迁移途径和突触联系的神经细胞类型。我们研究了c-kit和KL RNA及蛋白质产物在小鼠出生后小脑发育中的表达模式。在成年小脑中,c-kit RNA和蛋白质表达在篮状细胞、星状细胞和高尔基神经元中明显。最引人注目的是,c-kit蛋白在形成缠绕浦肯野细胞胞体和浦肯野细胞轴突起始段的“篮状”和“钳状”结构的篮状细胞轴突中表达。KL RNA表达在浦肯野细胞中发现,KL蛋白在浦肯野细胞体和树突中检测到。可溶性KL蛋白也存在于表达c-kit的篮状细胞、星状细胞和高尔基细胞中,推测是配体-受体复合物内化的结果。在出生后发育过程中,高尔基神经元和浦肯野神经元中分别的c-kit和KL RNA及蛋白质表达在出生后第0天就很明显,并在随后持续存在。篮状细胞和星状细胞中的c-kit表达从出生时(第4天开始)就可检测到。这些结果提示c-kit受体系统在小脑出生后发育中起作用。