Rostral cerebellar malformation (rcm/rcm): a murine mutant to study regionalization of the cerebellum
1Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. eisenma1@jeflin.tju.edu
Abstract:
A recently described recessive mouse mutant, rostral cerebellar malformation (rcm/rcm), demonstrates a swaying gait at approximately 12 days of age (Lane et al. [1992] J. Hered. 83:315-318). The mutant cerebellar (Cb) phenotype consists of cerebellar tissue that extends rostrally, beyond the usual distinct anterior cerebellar boundary, into the midbrain (Lane et al. [1992] J. Hered. 83:315-318; Ackerman et al. [1997] Nature 386:838-842). Interestingly, the cerebellar ectopia occurs in the absence of any significant alterations in the distribution of nuclear groups within the brainstem. The ectopic Cb tissue is 1) adherent to the posterior and lateral aspects of the inferior colliculus and to the lateral aspect of the rostral brainstem and 2) contains acellular regions within the inner granular layer (igl) and ectopic, calbindin-immunoreactive Purkinje cells (PCs) deep to the igl. Within the Cb proper, PC organization, as revealed by zebrin II immunoreactivity, is generally normal. In the ectopic Cb tissue PCs also exhibit a banded zebrin distribution. Analysis of the spinocerebellar projection in the mutant suggests a lobular distribution similar to that seen in the normal mouse. Within the anterior region, however, the normal parasagittal banding pattern is somewhat obscured. Spinocerebellar innervation of the ectopic Cb tissue exists, but it is almost exclusively to the region adjacent to the caudal inferior colliculus. In conjunction with the recent finding that the mutation appears to affect a UNC-5-like receptor protein for netrin-1, a molecule that may be involved in axonal guidance and cell migration (Ackerman et al. [1997] Nature 386:838-842), our results suggest that this mutant is an important model for the analysis of cerebellar development and regionalization.
Insights
The rostral cerebellar malformation (rcm/rcm) mouse mutant exhibits cerebellar tissue extending into the midbrain, impacting gait. This model aids in understanding cerebellar development and netrin-1 signaling.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- A recessive mouse mutant, rostral cerebellar malformation (rcm/rcm), displays a swaying gait.
- The mutant exhibits cerebellar tissue extending rostrally into the midbrain, a condition termed cerebellar ectopia.
Purpose of the Study:
- To characterize the phenotype of the rcm/rcm mouse mutant.
- To investigate the developmental implications of cerebellar ectopia.
- To explore the role of netrin-1 signaling in cerebellar development.
Main Methods:
- Phenotypic analysis of the rcm/rcm mouse mutant.
- Histological examination of cerebellar and brainstem structures.
- Immunohistochemical staining for Purkinje cells (PCs) and zebrin II.
- Analysis of spinocerebellar projections.
Main Results:
- Cerebellar ectopia occurs without significant brainstem nuclear group alterations.
- Ectopic cerebellar tissue contains acellular regions and ectopic Purkinje cells.
- Purkinje cell organization within the cerebellum proper is largely normal, with banded zebrin distribution also present in ectopic tissue.
- Spinocerebellar projections innervate the ectopic tissue, primarily near the inferior colliculus.
Conclusions:
- The rcm/rcm mouse mutant is a valuable model for studying cerebellar development and regionalization.
- The mutation, affecting a UNC-5-like receptor for netrin-1, provides insights into axonal guidance and cell migration during cerebellar development.
