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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

Effects of Klf4-knockout on cell death and/or cell proliferation in the developing cerebellum.A) Cresyl-violet staining of wild-type and Klf4- cerebellum. The appearance of heterochromatic cells is a hallmark of the Klf4- EGL compared to the wildtype at E15.5 (black arrows). The proliferating cells were identified as having condensed heterochromatin in one of the phases of mitosis. b) and c) BrdU-staining demonstrates a reduced proliferation of EGL and RL cells in the Klf4- at E13.5. b) Immunolabeling of BrdU in the cerebellum and c) counting of BrdU+ cells at E13.5. Proliferative cells incorporate BrdU into newly synthesized DNA and become BrdU+. There is a decreased number of BrdU+ cells in the EGL (p<0.01) and RL (p<0.05) of the Klf4- cerebellum. BrdU+ cells were identified as a dark brown staining after histochemical reaction with DAB. Number of BrdU+ cells were compared with one-tail students’ T-test and results were represented with 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.g004: Effects of Klf4-knockout on cell death and/or cell proliferation in the developing cerebellum.A) Cresyl-violet staining of wild-type and Klf4- cerebellum. The appearance of heterochromatic cells is a hallmark of the Klf4- EGL compared to the wildtype at E15.5 (black arrows). The proliferating cells were identified as having condensed heterochromatin in one of the phases of mitosis. b) and c) BrdU-staining demonstrates a reduced proliferation of EGL and RL cells in the Klf4- at E13.5. b) Immunolabeling of BrdU in the cerebellum and c) counting of BrdU+ cells at E13.5. Proliferative cells incorporate BrdU into newly synthesized DNA and become BrdU+. There is a decreased number of BrdU+ cells in the EGL (p<0.01) and RL (p<0.05) of the Klf4- cerebellum. BrdU+ cells were identified as a dark brown staining after histochemical reaction with DAB. Number of BrdU+ cells were compared with one-tail students’ T-test and results were represented with p<0.05(*), p<0.01 (**) and p<0.001 (***). X-axis: EGL—external granular layer, RL-Rhombic lip, NE- neuroepithelium.

Mentions: When we examined the wild-type and Klf4- in Nissl stained material for gross cerebellar morphology, the size and general structure of the E13.5 and 15.5 mutant cerebellum are comparable to the wild-type. However, we observed more heterochromatic GCs in the Klf4-/- compared to its wild-type litter-mates suggesting a role of Klf4 in cell death and/or cell proliferation (Fig 4a). TUNEL and anti-Casp-3 immunostaining were performed to assess cell apoptosis in the Klf4-/- cerebellum. Few cells were undergoing apoptosis in either the wild-type or Klf4-/- cerebellum during early development; and no differences in apoptosis with TUNEL and Casp3 immunostaining were seen (data not shown).


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)

Effects of Klf4-knockout on cell death and/or cell proliferation in the developing cerebellum.A) Cresyl-violet staining of wild-type and Klf4- cerebellum. The appearance of heterochromatic cells is a hallmark of the Klf4- EGL compared to the wildtype at E15.5 (black arrows). The proliferating cells were identified as having condensed heterochromatin in one of the phases of mitosis. b) and c) BrdU-staining demonstrates a reduced proliferation of EGL and RL cells in the Klf4- at E13.5. b) Immunolabeling of BrdU in the cerebellum and c) counting of BrdU+ cells at E13.5. Proliferative cells incorporate BrdU into newly synthesized DNA and become BrdU+. There is a decreased number of BrdU+ cells in the EGL (p<0.01) and RL (p<0.05) of the Klf4- cerebellum. BrdU+ cells were identified as a dark brown staining after histochemical reaction with DAB. Number of BrdU+ cells were compared with one-tail students’ T-test and results were represented with 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.g004: Effects of Klf4-knockout on cell death and/or cell proliferation in the developing cerebellum.A) Cresyl-violet staining of wild-type and Klf4- cerebellum. The appearance of heterochromatic cells is a hallmark of the Klf4- EGL compared to the wildtype at E15.5 (black arrows). The proliferating cells were identified as having condensed heterochromatin in one of the phases of mitosis. b) and c) BrdU-staining demonstrates a reduced proliferation of EGL and RL cells in the Klf4- at E13.5. b) Immunolabeling of BrdU in the cerebellum and c) counting of BrdU+ cells at E13.5. Proliferative cells incorporate BrdU into newly synthesized DNA and become BrdU+. There is a decreased number of BrdU+ cells in the EGL (p<0.01) and RL (p<0.05) of the Klf4- cerebellum. BrdU+ cells were identified as a dark brown staining after histochemical reaction with DAB. Number of BrdU+ cells were compared with one-tail students’ T-test and results were represented with p<0.05(*), p<0.01 (**) and p<0.001 (***). X-axis: EGL—external granular layer, RL-Rhombic lip, NE- neuroepithelium.
Mentions: When we examined the wild-type and Klf4- in Nissl stained material for gross cerebellar morphology, the size and general structure of the E13.5 and 15.5 mutant cerebellum are comparable to the wild-type. However, we observed more heterochromatic GCs in the Klf4-/- compared to its wild-type litter-mates suggesting a role of Klf4 in cell death and/or cell proliferation (Fig 4a). TUNEL and anti-Casp-3 immunostaining were performed to assess cell apoptosis in the Klf4-/- cerebellum. Few cells were undergoing apoptosis in either the wild-type or Klf4-/- cerebellum during early development; and no differences in apoptosis with TUNEL and Casp3 immunostaining were seen (data not shown).

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