RESUMEN
Infiltration of the endothelial layer of the blood-brain barrier by leukocytes plays a critical role in health and disease. When passing through the endothelial layer during the diapedesis process lymphocytes can either follow a paracellular route or a transcellular one. There is a debate whether these two processes constitute one mechanism, or they form two evolutionary distinct migration pathways. We used artificial intelligence, phylogenetic analysis, HH search, ancestor sequence reconstruction to investigate further this intriguing question. We found that the two systems share several ancient components, such as RhoA protein that plays a critical role in controlling actin movement in both mechanisms. However, some of the key components differ between these two transmigration processes. CAV1 genes emerged during Trichoplax adhaerens, and it was only reported in transcellular process. Paracellular process is dependent on PECAM1. PECAM1 emerged from FASL5 during Zebrafish divergence. Lastly, both systems employ late divergent genes such as ICAM1 and VECAM1. Taken together, our results suggest that these two systems constitute two different mechanical sensing mechanisms of immune cell infiltrations of the brain, yet these two systems are connected. We postulate that the mechanical properties of the cellular polarity is the main driving force determining the migration pathway. Our analysis indicates that both systems coevolved with immune cells, evolving to a higher level of complexity in association with the evolution of the immune system.
Asunto(s)
Células Endoteliales/metabolismo , Leucocitos/metabolismo , Proteínas/genética , Migración Transcelular de la Célula/genética , Transcriptoma , Migración Transendotelial y Transepitelial/genética , Animales , Evolución Biológica , Barrera Hematoencefálica/citología , Barrera Hematoencefálica/metabolismo , Caenorhabditis elegans/clasificación , Caenorhabditis elegans/citología , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Pollos/clasificación , Pollos/genética , Pollos/metabolismo , Ciona intestinalis/clasificación , Ciona intestinalis/citología , Ciona intestinalis/genética , Ciona intestinalis/metabolismo , Drosophila melanogaster/clasificación , Drosophila melanogaster/citología , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Células Endoteliales/citología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ontología de Genes , Humanos , Leucocitos/citología , Ratones , Pan troglodytes/clasificación , Pan troglodytes/genética , Pan troglodytes/metabolismo , Petromyzon/clasificación , Petromyzon/genética , Petromyzon/metabolismo , Filogenia , Placozoa/clasificación , Placozoa/citología , Placozoa/genética , Placozoa/metabolismo , Proteínas/clasificación , Proteínas/metabolismo , Anémonas de Mar/clasificación , Anémonas de Mar/citología , Anémonas de Mar/genética , Anémonas de Mar/metabolismo , Tiburones/clasificación , Tiburones/genética , Tiburones/metabolismo , Pez Cebra/clasificación , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment, the haematopoietic niche, which regulates HSPC behaviour1,2. The location of this niche varies across species, but the evolutionary pressures that drive HSPCs to different microenvironments remain unknown. The niche is located in the bone marrow in adult mammals, whereas it is found in other locations in non-mammalian vertebrates, for example, in the kidney marrow in teleost fish. Here we show that a melanocyte umbrella above the kidney marrow protects HSPCs against ultraviolet light in zebrafish. Because mutants that lack melanocytes have normal steady-state haematopoiesis under standard laboratory conditions, we hypothesized that melanocytes above the stem cell niche protect HSPCs against ultraviolet-light-induced DNA damage. Indeed, after ultraviolet-light irradiation, unpigmented larvae show higher levels of DNA damage in HSPCs, as indicated by staining of cyclobutane pyrimidine dimers and have reduced numbers of HSPCs, as shown by cmyb (also known as myb) expression. The umbrella of melanocytes associated with the haematopoietic niche is highly evolutionarily conserved in aquatic animals, including the sea lamprey, a basal vertebrate. During the transition from an aquatic to a terrestrial environment, HSPCs relocated into the bone marrow, which is protected from ultraviolet light by the cortical bone around the marrow. Our studies reveal that melanocytes above the haematopoietic niche protect HSPCs from ultraviolet-light-induced DNA damage in aquatic vertebrates and suggest that during the transition to terrestrial life, ultraviolet light was an evolutionary pressure affecting the location of the haematopoietic niche.
Asunto(s)
Evolución Biológica , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de la radiación , Melanocitos/citología , Melanocitos/efectos de la radiación , Nicho de Células Madre/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Animales , Organismos Acuáticos/clasificación , Citoprotección/efectos de la radiación , Daño del ADN/efectos de la radiación , Riñón , Mutación , Petromyzon/clasificación , Filogenia , Dímeros de Pirimidina/efectos de la radiación , Nicho de Células Madre/fisiología , Pez Cebra/clasificación , Pez Cebra/genéticaRESUMEN
The hindbrain is a vertebrate-specific embryonic structure of the central nervous system formed by iterative transitory units called rhombomeres (r). Rhombomeric cells are segregated by interhombomeric boundaries which are prefigured by sharp gene expression borders. The positioning of the first molecular boundary within the hindbrain (the prospective r4/r5 boundary) responds to the expression of an Iroquois (Irx) gene in the anterior (r4) and the gene vHnf1 at the posterior (r5). However, while Irx3 is expressed anteriorly in amniotes, a novel Irx gene, iro7, acts in teleosts. To assess the evolutionary history of the genes responsible for the positioning of the r4/r5 boundary in vertebrates, we have stepped outside the gnathostomes to investigate these genes in the agnathans Lethenteron japonicum and Petromyzon marinus. We identified one representative of the Hnf1 family in agnathans. Its expression pattern recapitulates that of vHnf1 and Hnf1 in higher vertebrates. Our phylogenetic analysis places this gene basal to gnathostome Hnf1 and vHnf1 genes. We propose that the duplication of an ancestral hnf1 gene present in the common ancestor of agnathans and gnathostomes gave rise to the two genes found in gnathostomes. We have also amplified 3 Irx genes in L. japonicum: LjIrxA, LjIrxC, LjIrxD. The expression pattern of LjIrxA (the agnathan Irx1/3 ortholog) resembles those of Irx3 or iro7 in gnathostomes. We propose that an Irx/hnf1 pair already present in early vertebrates positioned the r4/r5 boundary and that gene duplications occurred in these gene families after the divergence of the agnathans.
Asunto(s)
Evolución Molecular , Proteínas de Peces/genética , Proteínas de Homeodominio/genética , Lampreas/embriología , Lampreas/genética , Rombencéfalo/embriología , Secuencia de Aminoácidos , Animales , Tipificación del Cuerpo , Embrión no Mamífero/embriología , Proteínas de Peces/metabolismo , Duplicación de Gen , Regulación del Desarrollo de la Expresión Génica , Genes Homeobox , Factor Nuclear 1 del Hepatocito/genética , Lampreas/clasificación , Datos de Secuencia Molecular , Familia de Multigenes , Petromyzon/clasificación , Petromyzon/embriología , Petromyzon/genética , Filogenia , Alineación de Secuencia , Vertebrados/embriología , Vertebrados/genéticaRESUMEN
The interphotoreceptor retinoid-binding protein (IRBP) coding gene has been used with success for the large-scale phylogeny of mammals. However, its phylogenetic worth had not been explored in Actinopterygians. We explored the evolution of the structure of the gene and compared the structure predicted from known sequences with that of a basal vertebrate lineage, the sea lamprey Petromyzon marinus. This sequence is described here for the first time. The structure made up of four tandem repeats (or modules) arranged in a single gene, as present in Chondrichthyes (sharks and rays) and tetrapods, is also present in sea lamprey. In teleosts, one to two paralogous copies of IRBP gene have been identified depending on the genomes. When the sequences from all modules for a wide sampling of vertebrates are compared and analyzed, all sequences previously assigned to a particular module appear to be clustered together, suggesting that the divergence among modules is older than the split between lampreys and other vertebrates. Finally, 92 acanthomorph teleosts were sequenced for the partial module 1 of the gene 2 (713 bp) to assess for the first time the use of this marker for the systematic studies of the Teleostei. The partial sequence is slightly more variable than other markers currently used for this group, and the resulting trees from our sequences recover most of the clades described in the recent molecular multi-marker studies of the Acanthomorpha. We recommend the use of partial sequences from the IRBP gene 2 as a marker for phylogenetic inference in teleosts.