Abstract
The role of transcription factors in regulating the development of midbrain dopaminergic (mDA) neurons is intensively studied owing to the involvement of these neurons in diverse neurological disorders. Here we demonstrate novel roles for the forkhead/winged helix transcription factors Foxa1 and Foxa2 in the specification and differentiation of mDA neurons by analysing the phenotype of Foxa1 and Foxa2 single- and double-mutant mouse embryos. During specification, Foxa1 and Foxa2 regulate the extent of neurogenesis in mDA progenitors by positively regulating Ngn2 (Neurog2) expression. Subsequently, Foxa1 and Foxa2 regulate the expression of Nurr1 (Nr4a2) and engrailed 1 in immature neurons and the expression of aromatic L-amino acid decarboxylase and tyrosine hydroxylase in mature neurons during early and late differentiation of midbrain dopaminergic neurons. Interestingly, genetic evidence indicates that these functions require different gene dosages of Foxa1 and Foxa2. Altogether, our results demonstrate that Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner.
| Original language | English |
|---|---|
| Pages (from-to) | 2761-2769 |
| Number of pages | 9 |
| Journal | Development |
| Volume | 134 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - Aug 2007 |
Fingerprint
Keywords
- Cell fate specification
- Differentiation
- Dopaminergic
- Forkhead genes
- Gene dosage
- Midbrain
ASJC Scopus subject areas
- Anatomy
- Cell Biology
Cite this
Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. / Ferri, Anna L M; Lin, Wei; Mavromatakis, Yannis E.; Wang, Julie C.; Sasaki, Hiroshi; Whitsett, Jeffrey A.; Ang, Siew Lan.
In: Development, Vol. 134, No. 15, 08.2007, p. 2761-2769.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner
AU - Ferri, Anna L M
AU - Lin, Wei
AU - Mavromatakis, Yannis E.
AU - Wang, Julie C.
AU - Sasaki, Hiroshi
AU - Whitsett, Jeffrey A.
AU - Ang, Siew Lan
PY - 2007/8
Y1 - 2007/8
N2 - The role of transcription factors in regulating the development of midbrain dopaminergic (mDA) neurons is intensively studied owing to the involvement of these neurons in diverse neurological disorders. Here we demonstrate novel roles for the forkhead/winged helix transcription factors Foxa1 and Foxa2 in the specification and differentiation of mDA neurons by analysing the phenotype of Foxa1 and Foxa2 single- and double-mutant mouse embryos. During specification, Foxa1 and Foxa2 regulate the extent of neurogenesis in mDA progenitors by positively regulating Ngn2 (Neurog2) expression. Subsequently, Foxa1 and Foxa2 regulate the expression of Nurr1 (Nr4a2) and engrailed 1 in immature neurons and the expression of aromatic L-amino acid decarboxylase and tyrosine hydroxylase in mature neurons during early and late differentiation of midbrain dopaminergic neurons. Interestingly, genetic evidence indicates that these functions require different gene dosages of Foxa1 and Foxa2. Altogether, our results demonstrate that Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner.
AB - The role of transcription factors in regulating the development of midbrain dopaminergic (mDA) neurons is intensively studied owing to the involvement of these neurons in diverse neurological disorders. Here we demonstrate novel roles for the forkhead/winged helix transcription factors Foxa1 and Foxa2 in the specification and differentiation of mDA neurons by analysing the phenotype of Foxa1 and Foxa2 single- and double-mutant mouse embryos. During specification, Foxa1 and Foxa2 regulate the extent of neurogenesis in mDA progenitors by positively regulating Ngn2 (Neurog2) expression. Subsequently, Foxa1 and Foxa2 regulate the expression of Nurr1 (Nr4a2) and engrailed 1 in immature neurons and the expression of aromatic L-amino acid decarboxylase and tyrosine hydroxylase in mature neurons during early and late differentiation of midbrain dopaminergic neurons. Interestingly, genetic evidence indicates that these functions require different gene dosages of Foxa1 and Foxa2. Altogether, our results demonstrate that Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner.
KW - Cell fate specification
KW - Differentiation
KW - Dopaminergic
KW - Forkhead genes
KW - Gene dosage
KW - Midbrain
UR - http://www.scopus.com/inward/record.url?scp=34548186224&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548186224&partnerID=8YFLogxK
U2 - 10.1242/dev.000141
DO - 10.1242/dev.000141
M3 - Article
C2 - 17596284
AN - SCOPUS:34548186224
VL - 134
SP - 2761
EP - 2769
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 15
ER -