Lkb1 regulates granule cell migration and cortical folding of the cerebellar cortex
| Autor: | Ying Litingtung, Jonathan T. Fleming, Chin Chiang, Kaitlyn E. Ryan, Frances Y. Cheng, Patrick S. Kim, Emily Brignola |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell division Organogenesis Mutant Nerve Tissue Proteins AMP-Activated Protein Kinases Protein Serine-Threonine Kinases Biology Cytoplasmic Granules Article Cerebellar Cortex Mice 03 medical and health sciences Cell Movement medicine Animals Hedgehog Proteins Molecular Biology Gyrification Neurons Kinase Granule (cell biology) Cell Differentiation Cell Biology Anatomy Granule cell Hedgehog signaling pathway Cell biology 030104 developmental biology medicine.anatomical_structure Cerebellar cortex Cell Division Signal Transduction Developmental Biology |
| Zdroj: | Developmental Biology. 432:165-177 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2017.09.036 |
| Popis: | Cerebellar growth and foliation require the Hedgehog-driven proliferation of granule cell precursors (GCPs) in the external granule layer (EGL). However, that increased or extended GCP proliferation generally does not elicit ectopic folds suggests that additional determinants control cortical expansion and foliation during cerebellar development. Here, we find that genetic loss of the serine-threonine kinase Liver Kinase B1 (Lkb1) in GCPs increased cerebellar cortical size and foliation independent of changes in proliferation or Hedgehog signaling. This finding is unexpected given that Lkb1 has previously shown to be critical for Hedgehog pathway activation in cultured cells. Consistent with unchanged proliferation rate of GCPs, the cortical expansion of Lkb1 mutants is accompanied by thinning of the EGL. The plane of cell division, which has been implicated in diverse processes from epithelial surface expansions to gyrification of the human cortex, remains unchanged in the mutants when compared to wild-type controls. However, we find that Lkb1 mutants display delayed radial migration of post-mitotic GCPs that coincides with increased cortical size, suggesting that aberrant cell migration may contribute to the cortical expansion and increase foliation. Taken together, our results reveal an important role for Lkb1 in regulating cerebellar cortical size and foliation in a Hedgehog-independent manner. |
| Databáze: | OpenAIRE |
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