Limits...
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.

Show MeSH

Related in: MedlinePlus

Characterization of Mpl-positive cells. (A) Co-localization of Mpl and the pan-neuronal marker NeuN. Almost all Mpl-positive cells (green) are NeuN+ neurons (red) with the exception of cerebellar white matter. (B) Double-labelling of sections for Mpl and NeuroD, an early marker of granule cells. Mpl (green) does not overlap with NeuroD (red) in the cerebellum or in the hippocampus. (C) Expression of Mpl and the astrocyte marker GFAP in different brain regions at P0, P7 and in the adult brain. There is no overlap between Mpl (green) and GFAP (red). cp - cortical plate; egl - external granule layer; gcl - granule cell layer; h - hippocampus; wm - white matter. Scale bars: 20 μm in A and B, 50 μm in C.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2921376&req=5

Figure 4: Characterization of Mpl-positive cells. (A) Co-localization of Mpl and the pan-neuronal marker NeuN. Almost all Mpl-positive cells (green) are NeuN+ neurons (red) with the exception of cerebellar white matter. (B) Double-labelling of sections for Mpl and NeuroD, an early marker of granule cells. Mpl (green) does not overlap with NeuroD (red) in the cerebellum or in the hippocampus. (C) Expression of Mpl and the astrocyte marker GFAP in different brain regions at P0, P7 and in the adult brain. There is no overlap between Mpl (green) and GFAP (red). cp - cortical plate; egl - external granule layer; gcl - granule cell layer; h - hippocampus; wm - white matter. Scale bars: 20 μm in A and B, 50 μm in C.

Mentions: To characterize the cells, which express Mpl in the brain, we performed double immunohistochemistry with antibodies directed against Mpl as well as with established markers for neurons and astrocytes. All brain areas on parasagittal sections through the middle of the brain were examined for a possible overlap. The majority of Mpl-positive cells in the developing brain co-expressed the pan-neuronal marker NeuN with one exception: Mpl-expressing cells in the cerebellar white matter did not co-express NeuN (Figure 4A), indicating their possible glial origin. Since the Mpl-positive cells appeared in the brain during the generative period of small granule cells, we also performed double labelling of Mpl with the early granule cell marker NeuroD, but found no overlap in any of the examined regions (see Figure 4B for representative examples).


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)

Characterization of Mpl-positive cells. (A) Co-localization of Mpl and the pan-neuronal marker NeuN. Almost all Mpl-positive cells (green) are NeuN+ neurons (red) with the exception of cerebellar white matter. (B) Double-labelling of sections for Mpl and NeuroD, an early marker of granule cells. Mpl (green) does not overlap with NeuroD (red) in the cerebellum or in the hippocampus. (C) Expression of Mpl and the astrocyte marker GFAP in different brain regions at P0, P7 and in the adult brain. There is no overlap between Mpl (green) and GFAP (red). cp - cortical plate; egl - external granule layer; gcl - granule cell layer; h - hippocampus; wm - white matter. Scale bars: 20 μm in A and B, 50 μm in C.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Characterization of Mpl-positive cells. (A) Co-localization of Mpl and the pan-neuronal marker NeuN. Almost all Mpl-positive cells (green) are NeuN+ neurons (red) with the exception of cerebellar white matter. (B) Double-labelling of sections for Mpl and NeuroD, an early marker of granule cells. Mpl (green) does not overlap with NeuroD (red) in the cerebellum or in the hippocampus. (C) Expression of Mpl and the astrocyte marker GFAP in different brain regions at P0, P7 and in the adult brain. There is no overlap between Mpl (green) and GFAP (red). cp - cortical plate; egl - external granule layer; gcl - granule cell layer; h - hippocampus; wm - white matter. Scale bars: 20 μm in A and B, 50 μm in C.
Mentions: To characterize the cells, which express Mpl in the brain, we performed double immunohistochemistry with antibodies directed against Mpl as well as with established markers for neurons and astrocytes. All brain areas on parasagittal sections through the middle of the brain were examined for a possible overlap. The majority of Mpl-positive cells in the developing brain co-expressed the pan-neuronal marker NeuN with one exception: Mpl-expressing cells in the cerebellar white matter did not co-express NeuN (Figure 4A), indicating their possible glial origin. Since the Mpl-positive cells appeared in the brain during the generative period of small granule cells, we also performed double labelling of Mpl with the early granule cell marker NeuroD, but found no overlap in any of the examined regions (see Figure 4B for representative examples).

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