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Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system.

Ivanova A, Wuerfel J, Zhang J, Hoffmann O, Ballmaier M, Dame C - BMC Dev. Biol. (2010)

Bottom Line: Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons.From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord.Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neonatology, Charité - Universitätsmedizin, Germany.

ABSTRACT

Background: Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons. Mpl expression has been analysed in brain tissue on transcript level and in cultured primary rat neurons and astrocytes on protein level. Herein, we analysed Mpl expression in the developing and adult murine CNS by immunohistochemistry and investigated the brain of mice with homozygous Mpl deficiency (Mpl-/-) by MRI.

Results: Mpl was not detectable at developmental stages E12 to E15 in any resident cells of the CNS. From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord. However, major developmental changes became obvious: In the subventricular zone of the cerebral cortex Mpl expression occurred only during late gestation, while in the hippocampus Mpl expression was detectable for first time at stage P4. In the white matter of the cerebellum Mpl expression was restricted to the perinatal period. In the adult cerebellum, Mpl expression switched to Purkinje cell. The majority of other Mpl-positive cells were NeuN-positive neurons. None of the cells could be double-labelled with astrocyte marker GFAP. Mpl-/- mice showed no gross abnormalities of the brain.

Conclusions: Our data locate Mpl expression to neurons at different subdivisions of the spinal cord, rhombencephalon, midbrain and prosencephalon. Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum.

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Detection of Mpl-positive cells in the embryonic central nervous system. Schematic drawings show the positions of the micrographs. During early embryonic development both brain and spinal cord are devoid of Mpl labelling. Left column shows representative examples at E12 (A) and E15 (B, C). The green labelling on the blood vessels is unspecific as it also labels negative control sections incubated without the primary antibody. By embryonic day 18 (E18) numerous Mpl-positive cells appear in the inner cortical plate, subventricular zone of the fourth ventricle and parenchymal regions of rhombencephalon (D-G). At P0 the number of Mpl positive cells reaches its peak, spreading throughout many brain regions (I, J, K), including the subventricular zone of the lateral ventricles (H). Dorsal is up, anterior to the left. chp - choroid plexus; cp - cortical plate; dcn - dorsal cochlear nucleus; h - hippocampus; svz - subventriclar zone; wm - white matter; IV - forth ventricle. Scale bar 50 μm.
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Figure 2: Detection of Mpl-positive cells in the embryonic central nervous system. Schematic drawings show the positions of the micrographs. During early embryonic development both brain and spinal cord are devoid of Mpl labelling. Left column shows representative examples at E12 (A) and E15 (B, C). The green labelling on the blood vessels is unspecific as it also labels negative control sections incubated without the primary antibody. By embryonic day 18 (E18) numerous Mpl-positive cells appear in the inner cortical plate, subventricular zone of the fourth ventricle and parenchymal regions of rhombencephalon (D-G). At P0 the number of Mpl positive cells reaches its peak, spreading throughout many brain regions (I, J, K), including the subventricular zone of the lateral ventricles (H). Dorsal is up, anterior to the left. chp - choroid plexus; cp - cortical plate; dcn - dorsal cochlear nucleus; h - hippocampus; svz - subventriclar zone; wm - white matter; IV - forth ventricle. Scale bar 50 μm.

Mentions: Our analysis revealed no specific Mpl labelling in any resident cells of the CNS at developmental stages E12 and E15 (Figure 2A-C). Signals detected in the dorsal medulla at E12 may be an artefact (Figure 2A), since these structures were larger in size than normal neuroblasts at E12 and had ragged shape; they were also detected on consecutive sections incubated with secondary antibody alone.


Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system.

Ivanova A, Wuerfel J, Zhang J, Hoffmann O, Ballmaier M, Dame C - BMC Dev. Biol. (2010)

Detection of Mpl-positive cells in the embryonic central nervous system. Schematic drawings show the positions of the micrographs. During early embryonic development both brain and spinal cord are devoid of Mpl labelling. Left column shows representative examples at E12 (A) and E15 (B, C). The green labelling on the blood vessels is unspecific as it also labels negative control sections incubated without the primary antibody. By embryonic day 18 (E18) numerous Mpl-positive cells appear in the inner cortical plate, subventricular zone of the fourth ventricle and parenchymal regions of rhombencephalon (D-G). At P0 the number of Mpl positive cells reaches its peak, spreading throughout many brain regions (I, J, K), including the subventricular zone of the lateral ventricles (H). Dorsal is up, anterior to the left. chp - choroid plexus; cp - cortical plate; dcn - dorsal cochlear nucleus; h - hippocampus; svz - subventriclar zone; wm - white matter; IV - forth ventricle. Scale bar 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2921376&req=5

Figure 2: Detection of Mpl-positive cells in the embryonic central nervous system. Schematic drawings show the positions of the micrographs. During early embryonic development both brain and spinal cord are devoid of Mpl labelling. Left column shows representative examples at E12 (A) and E15 (B, C). The green labelling on the blood vessels is unspecific as it also labels negative control sections incubated without the primary antibody. By embryonic day 18 (E18) numerous Mpl-positive cells appear in the inner cortical plate, subventricular zone of the fourth ventricle and parenchymal regions of rhombencephalon (D-G). At P0 the number of Mpl positive cells reaches its peak, spreading throughout many brain regions (I, J, K), including the subventricular zone of the lateral ventricles (H). Dorsal is up, anterior to the left. chp - choroid plexus; cp - cortical plate; dcn - dorsal cochlear nucleus; h - hippocampus; svz - subventriclar zone; wm - white matter; IV - forth ventricle. Scale bar 50 μm.
Mentions: Our analysis revealed no specific Mpl labelling in any resident cells of the CNS at developmental stages E12 and E15 (Figure 2A-C). Signals detected in the dorsal medulla at E12 may be an artefact (Figure 2A), since these structures were larger in size than normal neuroblasts at E12 and had ragged shape; they were also detected on consecutive sections incubated with secondary antibody alone.

Bottom Line: Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons.From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord.Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neonatology, Charité - Universitätsmedizin, Germany.

ABSTRACT

Background: Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons. Mpl expression has been analysed in brain tissue on transcript level and in cultured primary rat neurons and astrocytes on protein level. Herein, we analysed Mpl expression in the developing and adult murine CNS by immunohistochemistry and investigated the brain of mice with homozygous Mpl deficiency (Mpl-/-) by MRI.

Results: Mpl was not detectable at developmental stages E12 to E15 in any resident cells of the CNS. From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord. However, major developmental changes became obvious: In the subventricular zone of the cerebral cortex Mpl expression occurred only during late gestation, while in the hippocampus Mpl expression was detectable for first time at stage P4. In the white matter of the cerebellum Mpl expression was restricted to the perinatal period. In the adult cerebellum, Mpl expression switched to Purkinje cell. The majority of other Mpl-positive cells were NeuN-positive neurons. None of the cells could be double-labelled with astrocyte marker GFAP. Mpl-/- mice showed no gross abnormalities of the brain.

Conclusions: Our data locate Mpl expression to neurons at different subdivisions of the spinal cord, rhombencephalon, midbrain and prosencephalon. Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum.

Show MeSH
Related in: MedlinePlus