Table 1.
Guide to Selected Differentiation Factors Implicated in the Development of Mesencephalic Dopaminergic Neurons
Protein | Abbreviations | Function | Floor/Base Plate Expression | Mid/Hindbrain Expression |
Sonic hedgehog | SHH | Secreted morphogen | √ | |
Fibroblast growth factor 8 | FGF8 | Secreted morphogen | √ | |
Wingless homologue 1 | WNT1 | Secreted morphogen | √ | √ |
Engrailed 1 and 2 | EN1, EN2 | Transcription factors | √ | √ |
LIM homeoboxa transcription factor 1 alpha, beta | LMX1a, b | Transcription factors | √ | √ |
Paired-like homeodomain1 transcription factor 3 | PITX3 | Transcription factor | √ | |
Orthodenticle homolog 2 | OTX2 | Transcription factor | √ | √ |
Paired box transcription factors 2 and 5 | PAX2, PAX5 | Transcription factors | √ | |
Gastrulation brain homeobox 2 | GBX2 | Transcription factor | √ | |
Nuclear receptor subfamily 4 | NR4a2/NURR1 | Nuclear orphan receptor | √ | |
MicroRNA 133bb | mir-133b | MicroRNA | mDA expression |
The homeobox is a conserved sequence of 180 DNA base pairs that codes for a segment of 60 amino acids that will bind to specific DNA regions. Transcription factors that include this sequence of amino acids are called homeodomain proteins, and the 60 amino acid segment is referred to as the “homeodomain.” The homeodomain was first recognized in proteins that regulate the formation of body parts in fruit flies. Mutations in a homeobox genes could transform one body segment into a different body part. A classic example is a mutation in the antennapedia gene that converts antennae on the head of a fruit fly into legs.48
MicroRNAs are a recently discovered class of RNA molecules that appear to play a critical role in the regulation of gene expression.49 mDA, mesoencephalic dopamine.