Expression of a Prrxl1 alternative splice variant during the development of the mouse nociceptive system.
BACKGROUND
Gene expression can be differentially regulated by alternatively spliced transcription factors, providing a mechanism for precise control of diverse morphogenetic events. The paired-type homedomain transcription factor Prrxl1 (formerly known as Drg11) was described as a key regulator of the differentiation of the spinal cord neuronal circuit dedicated to the processing of nociceptive information. Here, we report the characterization of a Prrxl1 alternative splice variant that we termed Prrxl1-b.


METHODS
Mouse Prrxl1 isoform mRNA sequences were obtained by Rapid Amplification cDNA Ends (RACE) analysis. The distribution and the amount of Prrxl1-b at different developmental ages were analyzed by in situ hybridization and quantitative real-time PCR, and compared with those of Prrxl1.


RESULTS
The amount of Prrxl1 was higher than that of the Prrxl1-b isoform both in the DRG and the spinal cord. Prrxl1-b contains the N-terminal homeodomain but differs from the previously identified Prrxl1 in the C-terminal part due to alternative mRNA processing. This results in the lack of the OAR domain in the Prrxl1-b primary structure. Prrxl1-b is exclusively localized in neurons primarily involved in the processing of the pain somatosensory modality. Prrxl1-b presents the same regional distribution pattern as Prrxl1, but differs as to the qualitative and quantitative expression profile at distinct developmental ages in the dorsal root ganglion and spinal cord.


CONCLUSIONS
We suggest that the tissue-specific role of the Prrxl1 gene may be sustained by an accurate balance in the ratio between the amount of Prrxl1 and its OAR-lacking variant, Prrxl1-b, which may be critical during nociceptive circuit development.
Rebelo
Sandra
S
IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.
Lopes
Cláudia
C
Lima
Deolinda
D
Reguenga
Carlos
C
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D009420:Nervous System / Q000196:embryology* / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D011247:Pregnancy; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C433766:Prrxl1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA