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Tracing lineages to uncover neuronal identity.

Panman L, Perlmann T - BMC Biol. (2011)

Bottom Line: Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis.One of the remaining questions concerns how different dopamine neuron subtypes are specified.A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the developing midbrain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ludwig Institute for Cancer Research Ltd, Stockholm, Sweden.

ABSTRACT
Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis. One of the remaining questions concerns how different dopamine neuron subtypes are specified. A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the developing midbrain.

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Related in: MedlinePlus

Acquisition of neurogenic potential in midbrain floorplate cells. From analysis of gene expression, the midbrain DA neuron progenitor domain can be subdivided into medial (DAM) and lateral (DAL) domains. Left, at early embryonic stages, medial DA progenitor cells resemble floorplate cells expressing high levels of Shh (pale gray). Right, downregulation of Shh (striped pale grey) in the medial progenitor domain at later stages in embryogenesis promotes neurogenesis from the medial progenitor domain.
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Figure 1: Acquisition of neurogenic potential in midbrain floorplate cells. From analysis of gene expression, the midbrain DA neuron progenitor domain can be subdivided into medial (DAM) and lateral (DAL) domains. Left, at early embryonic stages, medial DA progenitor cells resemble floorplate cells expressing high levels of Shh (pale gray). Right, downregulation of Shh (striped pale grey) in the medial progenitor domain at later stages in embryogenesis promotes neurogenesis from the medial progenitor domain.

Mentions: Other studies have also begun to define molecular differences between medial and lateral DA neuron progenitor cells that may relate to DA neuron subtype specification. A remarkable feature of the development of DA neurons is that they can be generated at the midbrain ventral midline from floorplate cells with glia-like characteristics. In contrast, floorplate cells within the ventral midline of the hindbrain and spinal cord are unable to give rise to neurons. Thus, the midbrain floorplate cells are unique in their neurogenic capacity. The DA neuron progenitor zone can be molecularly defined as floorplate cells expressing the cell surface protein Corin and Shh, the latter only expressed at high levels at early stages of development, together with more lateral neuronal progenitors that lack floorplate characteristics and selectively express the signaling protein Wnt1 (Figure 1). Both Shh and Wnt1 are critical signaling molecules with important functions for many types of developing neurons, including DA neurons. Interestingly, downregulation of Shh expression within the ventral midline has been shown to be essential for the acquisition of neurogenic potential of floorplate cells [10] as shown by the expression of pan-neuronal transcription factor Ngn2. In addition, a recent study demonstrated that the characteristic DA neuron transcription factor Lmx1a is important for the appropriate onset of neurogenesis from the midbrain floorplate cells, whereas the related transcription factor Lmx1b is selectively required for the generation of DA neurons from more lateral Wnt1-expressing progenitors [11].


Tracing lineages to uncover neuronal identity.

Panman L, Perlmann T - BMC Biol. (2011)

Acquisition of neurogenic potential in midbrain floorplate cells. From analysis of gene expression, the midbrain DA neuron progenitor domain can be subdivided into medial (DAM) and lateral (DAL) domains. Left, at early embryonic stages, medial DA progenitor cells resemble floorplate cells expressing high levels of Shh (pale gray). Right, downregulation of Shh (striped pale grey) in the medial progenitor domain at later stages in embryogenesis promotes neurogenesis from the medial progenitor domain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3141605&req=5

Figure 1: Acquisition of neurogenic potential in midbrain floorplate cells. From analysis of gene expression, the midbrain DA neuron progenitor domain can be subdivided into medial (DAM) and lateral (DAL) domains. Left, at early embryonic stages, medial DA progenitor cells resemble floorplate cells expressing high levels of Shh (pale gray). Right, downregulation of Shh (striped pale grey) in the medial progenitor domain at later stages in embryogenesis promotes neurogenesis from the medial progenitor domain.
Mentions: Other studies have also begun to define molecular differences between medial and lateral DA neuron progenitor cells that may relate to DA neuron subtype specification. A remarkable feature of the development of DA neurons is that they can be generated at the midbrain ventral midline from floorplate cells with glia-like characteristics. In contrast, floorplate cells within the ventral midline of the hindbrain and spinal cord are unable to give rise to neurons. Thus, the midbrain floorplate cells are unique in their neurogenic capacity. The DA neuron progenitor zone can be molecularly defined as floorplate cells expressing the cell surface protein Corin and Shh, the latter only expressed at high levels at early stages of development, together with more lateral neuronal progenitors that lack floorplate characteristics and selectively express the signaling protein Wnt1 (Figure 1). Both Shh and Wnt1 are critical signaling molecules with important functions for many types of developing neurons, including DA neurons. Interestingly, downregulation of Shh expression within the ventral midline has been shown to be essential for the acquisition of neurogenic potential of floorplate cells [10] as shown by the expression of pan-neuronal transcription factor Ngn2. In addition, a recent study demonstrated that the characteristic DA neuron transcription factor Lmx1a is important for the appropriate onset of neurogenesis from the midbrain floorplate cells, whereas the related transcription factor Lmx1b is selectively required for the generation of DA neurons from more lateral Wnt1-expressing progenitors [11].

Bottom Line: Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis.One of the remaining questions concerns how different dopamine neuron subtypes are specified.A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the developing midbrain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ludwig Institute for Cancer Research Ltd, Stockholm, Sweden.

ABSTRACT
Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis. One of the remaining questions concerns how different dopamine neuron subtypes are specified. A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the developing midbrain.

Show MeSH
Related in: MedlinePlus