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c-kit receptor and ligand expression in postnatal development of the mouse cerebellum suggests a function for c-kit
K Manova1, R F Bachvarova, E J Huang
1Molecular Biology Department, Sloan Kettering Institute, New York, New York 10021.
Abstract:
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.
Insights
The c-kit receptor and its ligand KL play a role in mouse cerebellar development. This study investigated their expression patterns in postnatal cerebellum development, revealing their presence in specific neuron types.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- The c-kit receptor tyrosine kinase and its ligand, KIT ligand (KL), are crucial for development.
- Mutations in the genes encoding c-kit (white spotting locus, W) and KL (steel locus, Sl) affect melanogenesis, gametogenesis, and hematopoiesis.
- While known targets exist, c-kit and KL are also expressed in the brain, including the cerebellum.
Purpose of the Study:
- To investigate the expression patterns of c-kit and KL RNA and protein during postnatal cerebellar development in mice.
- To determine the cellular localization and developmental timing of c-kit and KL expression in the cerebellum.
Main Methods:
- Analysis of c-kit and KL RNA and protein expression in mouse cerebellum at various postnatal stages.
- Immunohistochemistry and in situ hybridization techniques were likely employed.
Main Results:
- In adult cerebellum, c-kit was expressed in basket, stellate, and Golgi neurons, notably in basket cell axons forming structures around Purkinje cells.
- KL was expressed in Purkinje cells (RNA and protein) and also detected in c-kit-expressing neurons.
- Expression of both c-kit and KL was observed from early postnatal stages (day 0 or day 4) and persisted.
Conclusions:
- The c-kit receptor system is expressed in specific neuronal populations within the postnatal cerebellum.
- Findings suggest a potential role for the c-kit/KL signaling pathway in the postnatal development and function of the cerebellum.