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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 expression in the cerebellum and its co-expression with Pax6.a-c) Klf4 expression at: a) E13.5, b)E15.5, and c)E18.5. Immunohistochemistry of Klf4 in the developing cerebellum. Klf4 is expressed in the EGL of the cerebellum at E13.5 and E15.5 but virtually no expression is seen at E18.5 (black arrows). d-f) Co-expression of Klf4 and Pax6 in the EGL at E15.5. Immunofluorescence staining of Klf4 (green, d), Pax6 (red, e) and merged picture (f) in the developing cerebellum. Klf4 and Pax6 are co-expressed in the EGL (white arrows) of the cerebellum at E15.5. In (f), green arrow indicates EGL cells that express only Klf4, red arrow indicates cells in the cerebellar core that express only Pax6, and yellow arrow indicates EGL cells that co-express Klf4 and Pax6. EGL- external granular layer, NE—neuroepithelium, RL- Rhombic lip.
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pone.0134390.g001: Klf4 expression in the cerebellum and its co-expression with Pax6.a-c) Klf4 expression at: a) E13.5, b)E15.5, and c)E18.5. Immunohistochemistry of Klf4 in the developing cerebellum. Klf4 is expressed in the EGL of the cerebellum at E13.5 and E15.5 but virtually no expression is seen at E18.5 (black arrows). d-f) Co-expression of Klf4 and Pax6 in the EGL at E15.5. Immunofluorescence staining of Klf4 (green, d), Pax6 (red, e) and merged picture (f) in the developing cerebellum. Klf4 and Pax6 are co-expressed in the EGL (white arrows) of the cerebellum at E15.5. In (f), green arrow indicates EGL cells that express only Klf4, red arrow indicates cells in the cerebellar core that express only Pax6, and yellow arrow indicates EGL cells that co-express Klf4 and Pax6. EGL- external granular layer, NE—neuroepithelium, RL- Rhombic lip.

Mentions: To investigate Klf4 expression in the developing cerebellum, cerebellar tissues were collected from E13.5, E15.5 and E18.5 wild-type animals. RT-PCR and immunohistochemistry were performed on E13.5 and E15.5 cerebellar tissue to examine Klf4’s expression at RNA and protein levels, respectively. Klf4 is expressed in the wild-type cerebellum in E13.5, E15.5 and P0 (S1 Fig). Immunohistochemistry with anti-Klf4 was performed on E13.5 and E15.5 embryos. The staining in the cerebellum was much weaker than higher expressing regions such as the skin and the posterior rhombic lip (Fig 1b). Within the cerebellum, the main expression is in the cells of the EGL (Fig 1a). By E18.5, there was no detectible immunopositive staining for Klf4 (Fig 1c).


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 expression in the cerebellum and its co-expression with Pax6.a-c) Klf4 expression at: a) E13.5, b)E15.5, and c)E18.5. Immunohistochemistry of Klf4 in the developing cerebellum. Klf4 is expressed in the EGL of the cerebellum at E13.5 and E15.5 but virtually no expression is seen at E18.5 (black arrows). d-f) Co-expression of Klf4 and Pax6 in the EGL at E15.5. Immunofluorescence staining of Klf4 (green, d), Pax6 (red, e) and merged picture (f) in the developing cerebellum. Klf4 and Pax6 are co-expressed in the EGL (white arrows) of the cerebellum at E15.5. In (f), green arrow indicates EGL cells that express only Klf4, red arrow indicates cells in the cerebellar core that express only Pax6, and yellow arrow indicates EGL cells that co-express Klf4 and Pax6. EGL- external granular layer, NE—neuroepithelium, RL- Rhombic lip.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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pone.0134390.g001: Klf4 expression in the cerebellum and its co-expression with Pax6.a-c) Klf4 expression at: a) E13.5, b)E15.5, and c)E18.5. Immunohistochemistry of Klf4 in the developing cerebellum. Klf4 is expressed in the EGL of the cerebellum at E13.5 and E15.5 but virtually no expression is seen at E18.5 (black arrows). d-f) Co-expression of Klf4 and Pax6 in the EGL at E15.5. Immunofluorescence staining of Klf4 (green, d), Pax6 (red, e) and merged picture (f) in the developing cerebellum. Klf4 and Pax6 are co-expressed in the EGL (white arrows) of the cerebellum at E15.5. In (f), green arrow indicates EGL cells that express only Klf4, red arrow indicates cells in the cerebellar core that express only Pax6, and yellow arrow indicates EGL cells that co-express Klf4 and Pax6. EGL- external granular layer, NE—neuroepithelium, RL- Rhombic lip.
Mentions: To investigate Klf4 expression in the developing cerebellum, cerebellar tissues were collected from E13.5, E15.5 and E18.5 wild-type animals. RT-PCR and immunohistochemistry were performed on E13.5 and E15.5 cerebellar tissue to examine Klf4’s expression at RNA and protein levels, respectively. Klf4 is expressed in the wild-type cerebellum in E13.5, E15.5 and P0 (S1 Fig). Immunohistochemistry with anti-Klf4 was performed on E13.5 and E15.5 embryos. The staining in the cerebellum was much weaker than higher expressing regions such as the skin and the posterior rhombic lip (Fig 1b). Within the cerebellum, the main expression is in the cells of the EGL (Fig 1a). By E18.5, there was no detectible immunopositive staining for Klf4 (Fig 1c).

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