title: Evolutionary origins of lymphocytes: ensembles of T cell and B cell transcriptional regulators in a cartilaginous fish.
abstract: The evolutionary origins of lymphocytes can be traced by phylogenetic comparisons of key features. Homologs of rearranging TCR and Ig (B cell receptor) genes are present in jawed vertebrates, but have not been identified in other animal groups. In contrast, most of the transcription factors that are essential for the development of mammalian T and B lymphocytes belong to multigene families that are represented by members in the majority of the metazoans, providing a potential bridge to prevertebrate ancestral roles. This work investigates the structure and regulation of homologs of specific transcription factors known to regulate mammalian T and B cell development in a representative of the earliest diverging jawed vertebrates, the clearnose skate (Raja eglanteria). Skate orthologs of mammalian GATA-3, GATA-1, EBF-1, Pax-5, Pax-6, Runx2, and Runx3 have been characterized. GATA-3, Pax-5, Runx3, EBF-1, Spi-C, and most members of the Ikaros family are shown throughout ontogeny to be 1) coregulated with TCR or Ig expression, and 2) coexpressed with each other in combinations that for the most part correspond to known mouse T and B cell patterns, supporting conservation of function. These results indicate that multiple components of the gene regulatory networks that operate in mammalian T cell and B cell development were present in the common ancestor of the mammals and the cartilaginous fish. However, certain factors relevant to the B lineage differ in their tissue-specific expression patterns from their mouse counterparts, suggesting expanded or divergent B lineage characteristics or tissue specificity in these animals.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Michele K
authors.initials: MK
authors.lastname: Anderson
authors.forename: Rashmi
authors.initials: R
authors.lastname: Pant
authors.forename: Ann L
authors.initials: AL
authors.lastname: Miracle
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.forename: Carl A
authors.initials: CA
authors.lastname: Luer
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Walsh
authors.forename: Janice C
authors.initials: JC
authors.lastname: Telfer
authors.forename: Gary W
authors.initials: GW
authors.lastname: Litman
authors.forename: Ellen V
authors.initials: EV
authors.lastname: Rothenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017124:Conserved Sequence; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D019143:Evolution, Molecular; D050990:GATA3 Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D051757:PAX5 Transcription Factor; D016415:Sequence Alignment; D012860:Skates, Fish / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis / Q000302:isolation & purification; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D051757:PAX5 Transcription Factor; C493730:Runx3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors