Transcription factors involved in dopaminergic neurogenesis
| Nurr 1 |
| • Member of “zinc finger” superfamily of receptors; its subfamily includes nerve growth factor inducible B (NGFI-B) and neurone derived orphan receptor 1 (NOR-1)8 |
| • Human gene on 2q22–23; eight exons, spanning 8 kb. Murine, rat, and human genes have similar structures9–12 |
| • Full length mRNA has 3427 bases, 1794 are translated; the protein has 598 amino acids (66 kDa)16; splice variants exist—for example, Nurr 2—a novel cryptic exon located upstream in the Nurr 1 promoter region—and alternative splicing at exons 1, 2, and 613 |
| • Potential regulatory region contains consensus binding sites for nuclear factor κB (NF-κB), cAMP response element binding protein (CREB), and Sp191114 |
| • In the central nervous system (CNS) Nurr 1 expression occurs in the postmitotic late differential phase of dopaminergic precursor neuronal development,1516 detectable from rat embryonic day 10.517 |
| • Nurr 1 response elements: a single half site (AAAGGTCA) binds Nurr 1 as monomer; this is the same sequence as the NGFI-B response element78; a direct repeat (DR5) (AGGTCANNNAAAGGTCA) binds Nurr 1/RXR as a heterodimer, Nurr 1 homodimers, and the Nurr 1/NGFI-B heterodimer18–20 |
| • Nurr 1 response elements are found in tyrosine hydroxylase (AAAGGTCA),21 the dopamine transporter,22 and other molecules such as proopiomelanocortin23 |
| Ptx-3 |
| • Structurally related to pentaxins—for example, C reactive protein and serum amyloid P; subfamily includes Ptx-1 and Ptx-2, and homeobox proteins such as Otx-1 and Otx-22425 |
| • Human gene on chromosome 10.q25. has three exons26 |
| • cDNA has 1861 bp; protein has 381 amino acids25; Ptx-3 is also a secreted, acute phase protein |
| • mRNA induced in endothelial, hepatic, and fibroblastic cells by interleukin 1β (IL-1β) and tumour necrosis factor α, but not by IL-6 and interferon γ; raised serum concentrations after bacterial lipopolysaccharide injection252728 |
| • Expression is restricted in the CNS29 |
| • The Ptx-3 response element is GGCTTT |
| • There is a Ptx-3 response element in the tyrosine hydroxylase gene30 |
| • Mutations are associated with autosomal dominant cataracts26 |
| Lmx1b |
| • This transcription factor is related to members of the LIM family of homeobox proteins31 |
| • The human gene is on 9q34 and has eight exons32 |
| • Genetic mutations are associated with nail-patella syndrome33 |