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Kruppel-Like Factor 4 Regulates Granule Cell Pax6 Expression and Cell Proliferation in Early Cerebellar Development.

Zhang P, Ha T, Larouche M, Swanson D, Goldowitz D - PLoS ONE (2015)

Bottom Line: We find that Klf4 is expressed strongly in early granule cell progenitor development but tails-off considerably by the end of embryonic development.Klf4 is also co-expressed with Pax6 in these cells.This paper is the first to describe a role for Klf4 in the cerebellum and provides insight into this gene's function in neuronal development.

View Article: PubMed Central - PubMed

Affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada.

ABSTRACT
Kruppel-like factor 4 (Klf4) is a transcription factor that regulates many important cellular processes in stem cell biology, cancer, and development. We used histological and molecular methods to study the expression of Klf4 in embryonic development of the normal and Klf4 knockout cerebellum. We find that Klf4 is expressed strongly in early granule cell progenitor development but tails-off considerably by the end of embryonic development. Klf4 is also co-expressed with Pax6 in these cells. In the Klf4- mouse, which is perinatal lethal, Klf4 positively regulates Pax6 expression and regulates the proliferation of neuronal progenitors in the rhombic lip, external granular layer and the neuroepithelium. This paper is the first to describe a role for Klf4 in the cerebellum and provides insight into this gene's function in neuronal development.

No MeSH data available.


Related in: MedlinePlus

Klf4 has dual effects on the proliferation of epithelial cells in the cerebellum at E15.5.a) Immunolabeling of BrdU in the cerebellum and b) counting of BrdU+ cells at E15.5. There is an increased number of proliferating cells in the EGL (p<0.01) and RL (p<0.01), but a decreased number of proliferating cells in the NE (p<0.01) in the Klf4- cerebellum, indicated by a one-tailed Students’ T-test p<0.05(*), p<0.01 (**) and p<0.001 (***). X-axis: EGL—external granular layer, RL-Rhombic lip, NE- neuroepithelium.
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pone.0134390.g005: Klf4 has dual effects on the proliferation of epithelial cells in the cerebellum at E15.5.a) Immunolabeling of BrdU in the cerebellum and b) counting of BrdU+ cells at E15.5. There is an increased number of proliferating cells in the EGL (p<0.01) and RL (p<0.01), but a decreased number of proliferating cells in the NE (p<0.01) in the Klf4- cerebellum, indicated by a one-tailed Students’ T-test p<0.05(*), p<0.01 (**) and p<0.001 (***). X-axis: EGL—external granular layer, RL-Rhombic lip, NE- neuroepithelium.

Mentions: To look at cell proliferation, we used a short term (1 hour) BrdU exposure to assay cell proliferation in Klf4- embryos. In the E13.5 Klf4-/- cerebellum, we found a lower number of proliferating cells in the EGL (p<0.01) and RL (p<0.05) compared to wild-type litter-mates (Fig 4b and 4c). Furthermore, the EGL appears to be thinner and less extended in the Klf4- (Fig 4b; see also Fig 2a and 2b). The reduced granule cell proliferation at E13 in the Klf4 -/- suggests a positive regulatory role of Klf4 on early granule cell proliferation. However, this proliferative effect of Klf4 in the EGL is reversed at E15.5 when more proliferating cells are found in the Klf4- EGL (Fig 5, p<0.01) and RL (Fig 5, p<0.01). In addition, we also observed a decreased number of proliferating cells in the neuroepithelium (NE) where cerebellar interneurons are born at E15.5 (Fig 5b, p<0.01). This opposite effect on cell proliferation in the Klf4- hints at a differential (either direct or indirect) regulation of Klf4 in the two cerebellar neurogenic regions.


Kruppel-Like Factor 4 Regulates Granule Cell Pax6 Expression and Cell Proliferation in Early Cerebellar Development.

Zhang P, Ha T, Larouche M, Swanson D, Goldowitz D - PLoS ONE (2015)

Klf4 has dual effects on the proliferation of epithelial cells in the cerebellum at E15.5.a) Immunolabeling of BrdU in the cerebellum and b) counting of BrdU+ cells at E15.5. There is an increased number of proliferating cells in the EGL (p<0.01) and RL (p<0.01), but a decreased number of proliferating cells in the NE (p<0.01) in the Klf4- cerebellum, indicated by a one-tailed Students’ T-test p<0.05(*), p<0.01 (**) and p<0.001 (***). X-axis: EGL—external granular layer, RL-Rhombic lip, NE- neuroepithelium.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4520560&req=5

pone.0134390.g005: Klf4 has dual effects on the proliferation of epithelial cells in the cerebellum at E15.5.a) Immunolabeling of BrdU in the cerebellum and b) counting of BrdU+ cells at E15.5. There is an increased number of proliferating cells in the EGL (p<0.01) and RL (p<0.01), but a decreased number of proliferating cells in the NE (p<0.01) in the Klf4- cerebellum, indicated by a one-tailed Students’ T-test p<0.05(*), p<0.01 (**) and p<0.001 (***). X-axis: EGL—external granular layer, RL-Rhombic lip, NE- neuroepithelium.
Mentions: To look at cell proliferation, we used a short term (1 hour) BrdU exposure to assay cell proliferation in Klf4- embryos. In the E13.5 Klf4-/- cerebellum, we found a lower number of proliferating cells in the EGL (p<0.01) and RL (p<0.05) compared to wild-type litter-mates (Fig 4b and 4c). Furthermore, the EGL appears to be thinner and less extended in the Klf4- (Fig 4b; see also Fig 2a and 2b). The reduced granule cell proliferation at E13 in the Klf4 -/- suggests a positive regulatory role of Klf4 on early granule cell proliferation. However, this proliferative effect of Klf4 in the EGL is reversed at E15.5 when more proliferating cells are found in the Klf4- EGL (Fig 5, p<0.01) and RL (Fig 5, p<0.01). In addition, we also observed a decreased number of proliferating cells in the neuroepithelium (NE) where cerebellar interneurons are born at E15.5 (Fig 5b, p<0.01). This opposite effect on cell proliferation in the Klf4- hints at a differential (either direct or indirect) regulation of Klf4 in the two cerebellar neurogenic regions.

Bottom Line: We find that Klf4 is expressed strongly in early granule cell progenitor development but tails-off considerably by the end of embryonic development.Klf4 is also co-expressed with Pax6 in these cells.This paper is the first to describe a role for Klf4 in the cerebellum and provides insight into this gene's function in neuronal development.

View Article: PubMed Central - PubMed

Affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada.

ABSTRACT
Kruppel-like factor 4 (Klf4) is a transcription factor that regulates many important cellular processes in stem cell biology, cancer, and development. We used histological and molecular methods to study the expression of Klf4 in embryonic development of the normal and Klf4 knockout cerebellum. We find that Klf4 is expressed strongly in early granule cell progenitor development but tails-off considerably by the end of embryonic development. Klf4 is also co-expressed with Pax6 in these cells. In the Klf4- mouse, which is perinatal lethal, Klf4 positively regulates Pax6 expression and regulates the proliferation of neuronal progenitors in the rhombic lip, external granular layer and the neuroepithelium. This paper is the first to describe a role for Klf4 in the cerebellum and provides insight into this gene's function in neuronal development.

No MeSH data available.


Related in: MedlinePlus