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En1 and Wnt signaling in midbrain dopaminergic neuronal development.

Alves dos Santos MT, Smidt MP - Neural Dev (2011)

Bottom Line: Decades of research on the developmental mechanisms of the mesodiencephalic dopaminergic (mdDA) system have led to the identification of many signaling pathways and transcription factors critical in its development.The unraveling of these pathways will help fill in the pieces of the puzzle that today dominates neurodevelopment research: how to make and maintain a mdDA neuron.In the present review, we provide an overview of the mdDA system, the processes and signaling molecules involved in its genesis, with a focus on the transcription factor En1 and the canonical Wnt pathway, highlighting recent findings on their relevance--and interplay--in the development and maintenance of the mdDA system.

View Article: PubMed Central - HTML - PubMed

Affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neurosciences and Pharmacology, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.

ABSTRACT
Dopaminergic neurons of the ventral mesodiencephalon are affected in significant health disorders such as Parkinson's disease, schizophrenia, and addiction. The ultimate goal of current research endeavors is to improve the clinical treatment of such disorders, such as providing a protocol for cell replacement therapy in Parkinson's disease that will successfully promote the specific differentiation of a stem cell into a dopaminergic neuronal phenotype. Decades of research on the developmental mechanisms of the mesodiencephalic dopaminergic (mdDA) system have led to the identification of many signaling pathways and transcription factors critical in its development. The unraveling of these pathways will help fill in the pieces of the puzzle that today dominates neurodevelopment research: how to make and maintain a mdDA neuron. In the present review, we provide an overview of the mdDA system, the processes and signaling molecules involved in its genesis, with a focus on the transcription factor En1 and the canonical Wnt pathway, highlighting recent findings on their relevance--and interplay--in the development and maintenance of the mdDA system.

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Wnt signaling during the central nervous system and mesodiencephalic dopaminergic neuron development. (A) Wnt signaling is critical in embryonic development, controlling diverse processes, such as cell proliferation and cell polarity. It is involved during early central nervous system (CNS) development in gastrulation, early pattern formation, morphogenesis and precursor proliferation, in late CNS development in processes such as neuronal differentiation and migration, and in adult organisms, where it plays a central role in the maintenance of tissue homeostasis and stem cell regulation. Wnt signaling controls diverse processes, such as cell proliferation, cell polarity, cell death and cell fate specification Wnts can also function as morphogens in both short- and long-range signaling, modulating target cells in a dose- and distance-dependent manner. (B) Wnt signaling is involved in mesodiencephalic dopaminergic (mdDA) neuron development from early on, where it is involved in morphogenesis, and later on as well in mdDA differentiation.
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Figure 4: Wnt signaling during the central nervous system and mesodiencephalic dopaminergic neuron development. (A) Wnt signaling is critical in embryonic development, controlling diverse processes, such as cell proliferation and cell polarity. It is involved during early central nervous system (CNS) development in gastrulation, early pattern formation, morphogenesis and precursor proliferation, in late CNS development in processes such as neuronal differentiation and migration, and in adult organisms, where it plays a central role in the maintenance of tissue homeostasis and stem cell regulation. Wnt signaling controls diverse processes, such as cell proliferation, cell polarity, cell death and cell fate specification Wnts can also function as morphogens in both short- and long-range signaling, modulating target cells in a dose- and distance-dependent manner. (B) Wnt signaling is involved in mesodiencephalic dopaminergic (mdDA) neuron development from early on, where it is involved in morphogenesis, and later on as well in mdDA differentiation.

Mentions: Recent studies have provided us with a more complete picture of the dynamic expression patterns of Wnts, their receptors and co-factors during development and adulthood (for a review, see [157,158]). The expression of Wnt signaling components during development of the CNS has also been described. To begin with, many Fz receptors are expressed in the mouse brain [139,159], including Ryk, the lipoprotein receptor-related protein co-receptor [160] and the receptor tyrosine kinase-like orphan receptor (Ror) family [161]. Secondly, various Wnts are expressed in the developing CNS and peripheral nervous system, in overlapping and complementary patterns [162]. More and more evidence has surfaced corroborating the key role of Wnt signaling in the developing neural tube and brain [117]. Indeed, Wnt signaling seems to take part in most of the processes needed to generate a fully functional neuron (Figure 4A) from a neuronal stem cell, participating in early events, such as neuronal induction [163], anterior-posterior patterning and morphogenesis [164-167] and neuronal precursor proliferation [168-174], as well as in later processes, such as neuronal differentiation in the spinal cord [175], neuronal stem cells [176,177] and cortical neuronal precursors [178], neuronal cortical migration in mice [179], axon guidance in Drosophila [180] and in mice [181-183], synaptogenesis [184-186], synaptic differentiation [187,188], dendritogenesis [189,190] and neurogenesis in the telecephalon and hindbrain of adult mice [191-193].


En1 and Wnt signaling in midbrain dopaminergic neuronal development.

Alves dos Santos MT, Smidt MP - Neural Dev (2011)

Wnt signaling during the central nervous system and mesodiencephalic dopaminergic neuron development. (A) Wnt signaling is critical in embryonic development, controlling diverse processes, such as cell proliferation and cell polarity. It is involved during early central nervous system (CNS) development in gastrulation, early pattern formation, morphogenesis and precursor proliferation, in late CNS development in processes such as neuronal differentiation and migration, and in adult organisms, where it plays a central role in the maintenance of tissue homeostasis and stem cell regulation. Wnt signaling controls diverse processes, such as cell proliferation, cell polarity, cell death and cell fate specification Wnts can also function as morphogens in both short- and long-range signaling, modulating target cells in a dose- and distance-dependent manner. (B) Wnt signaling is involved in mesodiencephalic dopaminergic (mdDA) neuron development from early on, where it is involved in morphogenesis, and later on as well in mdDA differentiation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104484&req=5

Figure 4: Wnt signaling during the central nervous system and mesodiencephalic dopaminergic neuron development. (A) Wnt signaling is critical in embryonic development, controlling diverse processes, such as cell proliferation and cell polarity. It is involved during early central nervous system (CNS) development in gastrulation, early pattern formation, morphogenesis and precursor proliferation, in late CNS development in processes such as neuronal differentiation and migration, and in adult organisms, where it plays a central role in the maintenance of tissue homeostasis and stem cell regulation. Wnt signaling controls diverse processes, such as cell proliferation, cell polarity, cell death and cell fate specification Wnts can also function as morphogens in both short- and long-range signaling, modulating target cells in a dose- and distance-dependent manner. (B) Wnt signaling is involved in mesodiencephalic dopaminergic (mdDA) neuron development from early on, where it is involved in morphogenesis, and later on as well in mdDA differentiation.
Mentions: Recent studies have provided us with a more complete picture of the dynamic expression patterns of Wnts, their receptors and co-factors during development and adulthood (for a review, see [157,158]). The expression of Wnt signaling components during development of the CNS has also been described. To begin with, many Fz receptors are expressed in the mouse brain [139,159], including Ryk, the lipoprotein receptor-related protein co-receptor [160] and the receptor tyrosine kinase-like orphan receptor (Ror) family [161]. Secondly, various Wnts are expressed in the developing CNS and peripheral nervous system, in overlapping and complementary patterns [162]. More and more evidence has surfaced corroborating the key role of Wnt signaling in the developing neural tube and brain [117]. Indeed, Wnt signaling seems to take part in most of the processes needed to generate a fully functional neuron (Figure 4A) from a neuronal stem cell, participating in early events, such as neuronal induction [163], anterior-posterior patterning and morphogenesis [164-167] and neuronal precursor proliferation [168-174], as well as in later processes, such as neuronal differentiation in the spinal cord [175], neuronal stem cells [176,177] and cortical neuronal precursors [178], neuronal cortical migration in mice [179], axon guidance in Drosophila [180] and in mice [181-183], synaptogenesis [184-186], synaptic differentiation [187,188], dendritogenesis [189,190] and neurogenesis in the telecephalon and hindbrain of adult mice [191-193].

Bottom Line: Decades of research on the developmental mechanisms of the mesodiencephalic dopaminergic (mdDA) system have led to the identification of many signaling pathways and transcription factors critical in its development.The unraveling of these pathways will help fill in the pieces of the puzzle that today dominates neurodevelopment research: how to make and maintain a mdDA neuron.In the present review, we provide an overview of the mdDA system, the processes and signaling molecules involved in its genesis, with a focus on the transcription factor En1 and the canonical Wnt pathway, highlighting recent findings on their relevance--and interplay--in the development and maintenance of the mdDA system.

View Article: PubMed Central - HTML - PubMed

Affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neurosciences and Pharmacology, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.

ABSTRACT
Dopaminergic neurons of the ventral mesodiencephalon are affected in significant health disorders such as Parkinson's disease, schizophrenia, and addiction. The ultimate goal of current research endeavors is to improve the clinical treatment of such disorders, such as providing a protocol for cell replacement therapy in Parkinson's disease that will successfully promote the specific differentiation of a stem cell into a dopaminergic neuronal phenotype. Decades of research on the developmental mechanisms of the mesodiencephalic dopaminergic (mdDA) system have led to the identification of many signaling pathways and transcription factors critical in its development. The unraveling of these pathways will help fill in the pieces of the puzzle that today dominates neurodevelopment research: how to make and maintain a mdDA neuron. In the present review, we provide an overview of the mdDA system, the processes and signaling molecules involved in its genesis, with a focus on the transcription factor En1 and the canonical Wnt pathway, highlighting recent findings on their relevance--and interplay--in the development and maintenance of the mdDA system.

Show MeSH
Related in: MedlinePlus