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Pattern deformities and cell loss in Engrailed-2 mutant mice suggest two separate patterning events during cerebellar
B Kuemerle1, H Zanjani, A Joyner
1Alzheimer Research Laboratory, Case Western Reserve Medical School, Cleveland, Ohio 44106, USA.
Summary
The mouse Engrailed-2 gene is crucial for cerebellar development, influencing patterning and cell number. Its absence disrupts cerebellar foliation and alters expression patterns, suggesting a role in progenitor specification.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- The mouse Engrailed-2 (En-2) gene is a homolog of the fly engrailed gene.
- Null alleles of En-2 impact cerebellar anteroposterior (A/P) patterning, affecting cortical foliation and transgene expression boundaries.
- En-2 also influences transient mediolateral (M/L) expression patterns of En-1 and Wnt-7b during embryogenesis.
Purpose of the Study:
- To investigate the role of Engrailed-2 in cerebellar development and patterning.
- To analyze the effects of En-2 deficiency on cerebellar compartmentation markers and cell populations.
- To propose a model for En-2 function in specifying cerebellar progenitor number and adult cell count.
Main Methods:
- Examined three cerebellar compartmentation markers in En-2 mutant mice: Zebrin II, Ppath monoclonal antibodies, and L7lacZ transgene.
- Assessed temporal expression patterns, size, and spatial location of these markers in mutant versus wild-type mice.
- Performed cell counts to quantify major cell types within the olivocerebellar circuit.
Main Results:
- The temporal expression pattern of Zebrin II, Ppath, and L7lacZ was preserved in En-2 mutants, but band size and location differed.
- Mediolateral (M/L) pattern disturbances were observed across most cerebellar regions, unlike foliation abnormalities.
- A significant reduction (30-40%) in all major olivocerebellar circuit cell types was detected in En-2 mutants.
Conclusions:
- Engrailed-2 plays a role in the early specification of the cerebellar field, including the number of progenitor cells.
- En-2 contributes to specifying the adult cell number by influencing progenitor-derived clone size.
- Cerebellar lobule shape and Zebrin band configuration are likely determined by a post-neurogenesis patterning event, distinct from En-2's primary role.