Produção Nacional
Revisado por pares
Developmental Biology Takes on a Latin American Rhythm
2005; Cell Press; Volume: 122; Issue: 3 Linguagem: Inglês
10.1016/j.cell.2005.07.019
ISSN1097-4172
AutoresJosé Xavier‐Neto, Richard R. Behringer,
Tópico(s)Science, Research, and Medicine
ResumoAt a recent meeting in Latin America, developmental biologists discussed both traditional and not so traditional organisms that are valuable models for dissecting the intricate molecular mechanisms of development. At a recent meeting in Latin America, developmental biologists discussed both traditional and not so traditional organisms that are valuable models for dissecting the intricate molecular mechanisms of development. Latin America, the vast geopolitical region from Mexico to Cape Horn at the tip of South America, evokes images of the rain forests of the Amazon and snow-capped peaks of the Andes, ancient Incan and Mayan civilizations, Spanish and Portuguese colonialism, and iconic cities like Rio de Janeiro. Biological research in Latin America has traditionally focused on disciplines such as physiology, pharmacology, biochemistry, genetics, immunology, and parasitology as well as on agricultural and ecological sciences. However, an energetic group of developmental biologists has recently emerged from Argentina, Brazil, Chile, Ecuador, Mexico, Peru, Uruguay, and Venezuela. In 2003, this group, composed of senior scientists and young Latin American developmental biologists who recently returned to their home countries after training in America and Europe, founded the Latin American Society of Developmental Biology (LASDB). Led by their current president Roberto Mayor (University of Chile, Santiago/University College London), the LASDB (http://www.lasdb.org) is promoting developmental biology research in Latin America. The second International Meeting of the LASDB, organized by Ricardo Ramos (University of São Paulo-Ribeirão Preto, Brazil) and José Xavier-Neto (Heart Institute, InCor, University of São Paulo, Brazil), was held in May in Guarujá, Brazil, located on the coast just east of São Paulo. LASDB together with the Society for Developmental Biology (SDB) also offered a pre-meeting Short Course on primary model organisms in developmental biology (see Acknowledgments) to provide intensive training and facilitate interactions among graduate students and postdoctoral fellows from Latin and North America. The LASDB conference opened with a keynote address by Eric Wieschaus (Princeton University, New Jersey) followed by 33 speakers from Latin America, North America, and Europe. Wieschaus reported results from a global examination of the genes required at the mid-blastula transition in the fruit fly Drosophila. At this transition, cleavage mitoses halt, a cellular blastoderm forms, and gastrulation is initiated. It is at this point that complex interactions between maternal and zygotic gene products must be coordinated to ensure normal embryogenesis. Investigating embryos with chromosomal rearrangements by microarray analysis, Wieschaus’ group has created the first description of the genes that must be supplied from the zygotic genome for progression through the mid-blastula transition. These studies should yield insights into the relationships between zygotic gene expression, cell cycle control at the mid-blastula transition, and embryo morphogenesis. The classic model organisms of traditional developmental biology, such as the frog Xenopus, perhaps can be considered a product of the “Old World.” One of the major themes of both the Short Course and the LASDB meeting in the New World was the use of new model organisms to investigate developmental mechanisms. For decades, Xenopus laevis has dominated amphibian developmental biology and has influenced modern concepts of vertebrate development. We are all taught mesoderm and neural induction, the morphogenesis of gastrulation, and axial patterning using the Xenopus model, yet much is still unknown about early Xenopus embryonic development. Thus, the movies from Scott Fraser and his colleagues Russell Jacobs and Cyrus Papan (California Institute of Technology, Pasadena, California) showing live images of the internal aspects of Xenopus gastrulation were quite revealing. Their improved real-time live magnetic resonance imaging (MRI) technologies are able to visualize deep structures in the Xenopus embryo during gastrulation that were previously difficult to view because these embryos scatter light (Tyszka et al., 2005Tyszka J.M. Fraser S.E. Jacobs R.E. Magnetic resonance microscopy: recent advances and applications.Curr. Opin. Biotechnol. 2005; 16: 93-99Crossref PubMed Scopus (102) Google Scholar). These movies showed the dynamic internal details of involution, tissue interactions, and cavity morphogenesis. The ability to visualize the behavior of cells in live embryos should yield the clearest pictures of development in the most significant situation, the intact embryo. Fraser’s movies of Xenopus embryos promised a new understanding of amphibian development. However, a talk by Eugenia del Pino (Pontificia Universidad Católica del Ecuador, Quito, Ecuador) had the meeting participants questioning the broad applicability of the Xenopus model. del Pino studies the reproduction and development of a marsupial hylid frog, Gastrotheca riobambae (Figure 1A ), that inhabits the highlands of northern Ecuador. The reproduction and development of these terrestrial frogs is fascinating because they diverge from the common aquatic amphibian reproductive mode. In addition, the pattern of early development in this frog is highly modified, providing a unique opportunity for understanding vertebrate development (del Pino and Elinson, 1983del Pino E.M. Elinson R.P. Gastrulation produces an embryonic disc, a novel developmental pattern for frogs.Nature. 1983; 306: 589-591Crossref Scopus (54) Google Scholar). The eggs of Xenopus (∼1 mm in diameter) develop quickly after fertilization, whereas the eggs of Gastrotheca riobambae are larger (3 mm in diameter) and develop slowly after fertilization. The embryos of Gastrotheca develop inside a pouch located on the back of the female! About 120 eggs are placed inside the female’s pouch by the male at amplexus. Remarkably, it takes four months for Gastrotheca tadpoles to be released into the water. Other species of Gastrotheca produce fewer eggs that are as large as 10 mm in diameter, raising interesting biophysical issues about the mechanics of morphogen gradients in such large eggs. In those frogs, development inside the pouch advances to the frog stage, eliminating the aquatic larval stages altogether. Protected in the mother’s pouch, Gastrotheca development proceeds slowly. The first cleavage division occurs about 16 hr after fertilization, a time frame more similar to that of a mouse zygote than that of a Xenopus zygote. Cleavage becomes asynchronous after the 8-cell stage, suggesting the absence of the mid-blastula transition. Gastrulation begins at 7 days and is complete 14 days after fertilization. For comparison, mouse gastrulation begins on day 7 of development and concludes 1 day later. Gastrulation in Gastrotheca proceeds with involution at the blastopore lips. However, elongation and inflation of the archenteron occur only after closure of the blastopore. The small cells that accumulate in the blastopore lips form an embryonic disk. The embryonic disk expands 2 days after its formation and is associated with elongation and inflation of the archenteron and elongation of the notochord, as detected by the expression of the gene Brachyury (del Pino, 1996del Pino E.M. The expression of Brachyury (T) during gastrulation in the marsupial frog Gastrotheca riobambae.Dev. Biol. 1996; 177: 64-72Crossref PubMed Scopus (28) Google Scholar). The embryo develops from this disk of cells, over the large mass of cleaved yolk. Thus, gastrulation in Gastrotheca is the most divergent mode of frog gastrulation so far described. The study of early development in this slowly developing species facilitates the identification of the individual steps of the gastrulation process that otherwise occur simultaneously in the rapid developing embryos of Xenopus. It would be fascinating to analyze the unique gastrulating embryos of Gastrotheca with Fraser’s cutting-edge imaging techniques. One of the most abundant mammals in the New World tropics is the short-tailed fruit bat, Carollia perspicillata (Figure 1C). Next to rodents, bats compose the mammalian order with the second largest number of species (∼1,200), yet their embryology is largely unknown. Richard Behringer and colleagues (M.D. Anderson Cancer Center, Houston, Texas) have been developing a molecular embryology of bats using Carollia as their model (Cretekos et al., 2001Cretekos C.J. Rasweiler J.J. Behringer R.R. Comparative studies on limb morphogenesis in mice and bats: a functional genetic approach towards a molecular understanding of diversity in organ formation.Reprod. Fertil. Dev. 2001; 13: 691-695Crossref PubMed Google Scholar). At the meeting, Behringer discussed a Carollia embryo staging system using embryos derived from timed matings from a laboratory colony (Cretekos et al., 2005Cretekos C.J. Weatherbee S.D. Chen C.H. Badwaik N.K. Niswander L. Behringer R.R. Rasweiler 4th., J.J. Embryonic staging system for the short-tailed fruit bat, Carollia perspicillata, a model organism for the mammalian order Chiroptera, based upon timed pregnancies in captive-bred animals.Dev. Dyn. 2005; 233: 721-738Crossref PubMed Scopus (100) Google Scholar). This system, based on the Carnegie system for staging human embryos, provides a valuable method for staging embryos collected from the wild during the two Carollia breeding seasons on the island of Trinidad located just off the coast of Venezuela. Bats are unique among mammals because they have the ability of powered flight, possessing highly modified limbs that form wings. Behringer’s group is testing the hypothesis that variation in the expression of developmental control genes leads to organ diversity between species. To address this idea, they have focused on the Prx1 homeobox gene that regulates proximal-distal limb development in mice. Previous studies have identified a limb-specific transcriptional enhancer just 5′ of the mouse Prx1 locus (Martin and Olson, 2000Martin J.F. Olson E.N. Identification of a prx1 limb enhancer.Genesis. 2000; 26: 225-229Crossref PubMed Scopus (106) Google Scholar). Behringer reported the identification of the bat Prx1 limb enhancer using a transgenic mouse assay. He presented preliminary results on the altered limbs of mice created by gene targeting in embryonic stem cells that have the endogenous mouse Prx1 limb enhancer replaced by the bat Prx1 limb enhancer. This enhancer switch assay may become a key feature for comparative studies of the regulatory elements of developmental control genes between species. Brazil has an active group of researchers studying development, genetics, and behavior of bees (Figure 1D). Representing this group, Klaus Hartfelder (University of São Paulo-Ribeirão Preto, Brazil) spoke about social bees as eloquent examples of polyphenism, that is, how epigenetic/environmental cues work on identical genotypes to give rise to dramatically different phenotypes such as queen bees and sister workers. The biological bases of social bee’s impressive behavioral plasticity are to be found in their development, and Hartfelder pointed out that these mechanisms are beginning to be unraveled by comparative analyses of juvenile hormone and ecdysteroid titers as well as of the patterns of gene expression they elicit during larval development. These hormonal changes become integrated with basic patterns of metamorphosis regulation in the last larval instars of social bees to drive divergent differentiation into queen and worker phenotypes (Schmidt Capella and Hartfelder, 2002Schmidt Capella I.C. Hartfelder K. Juvenile-hormone-dependent interaction of actin and spectrin is crucial for polymorphic differentiation of the larval honey bee ovary.Cell Tissue Res. 2002; 307: 265-272Crossref PubMed Scopus (54) Google Scholar). Interestingly, vitellogenin, a reserve protein, seems to have acquired new functions, and its expression has become integrated into a regulatory circuitry that underlies the performance of different tasks during the adult life cycle (Amdam et al., 2003Amdam G.V. Norberg K. Hagen A. Omholt S.W. Social exploitation of vitellogenin.Proc. Natl. Acad. Sci. USA. 2003; 100: 1799-1802Crossref PubMed Scopus (261) Google Scholar). Microarray analyses of bee brain RNA, however, indicate that task switching involves complex changes in gene expression patterns. Progress in understanding the regulatory architecture of developmental and behavioral plasticity is turning the honey bee into a rich model organism. A major step forward can be expected as genome sequence information becomes available through the Honey Bee Genome Project (http://www.hgsc.bcm.tmc.edu/projects/honeybee). A second theme of the meeting was signaling pathways and how they are regulated during development and in disease states. The central event in the complex genetic pathway that patterns the dorsal-ventral axis of the Drosophila embryo is the entry of Dorsal protein into the nuclei of ventral cells. In the nucleus, Dorsal activates zygotic genes, such as short gastrulation (sog), that specify ventral fates and represses genes, such as decapentaplegic (dpp), that specify dorsal fates. Maternal expression of sog and dpp are also important for dorsal-ventral patterning. Again, acting in an antagonistic way, maternal Sog and Dpp act either downstream or parallel to the Toll receptor to modulate the levels of Cactus, the key regulator of Dorsal translocation into the nucleus. The mechanisms underlying the actions of maternal Sog and Dpp, however, have remained elusive. Helena Araujo (Federal University of Rio de Janeiro, Brazil) presented new data indicating that Sog and Dpp proteins are produced by follicle cells during mid-oogenesis in the fruit fly and are transferred to the perivitelline space during formation of the vitelline membrane. Araujo presented evidence that maternal Dpp is active both in the embryo and egg chamber and that metalloproteases that cleave Sog regulate the formation of embryonic and chorionic structures. Based on similar functions of sog and dpp action in the embryo and in the pupal wing, Araujo suggested a model in which an asymmetric distribution of Sog fragments with differential activities concentrates Dpp in dorsal regions of the ovarian follicle and embryo, resulting in a Dpp activity gradient that patterns the dorsal-ventral axis of the pre-blastoderm fly embryo (Araujo et al., 2003Araujo H. Negreiros E. Bier E. Integrins modulate Sog activity in the Drosophila wing.Development. 2003; 130: 3851-3864Crossref PubMed Scopus (28) Google Scholar). Interactions of signaling proteins with the extracellular matrix yield gradients of activity that direct embryonic development. Recently, the involvement of proteoglycans in early embryonic development has been clearly demonstrated by studies in various models, including Drosophila, zebrafish, and mouse (Lin, 2004Lin X. Functions of heparan sulfate proteoglycans in cell signaling during development.Development. 2004; 131: 6009-6021Crossref PubMed Scopus (500) Google Scholar). However, an understanding of the roles of specific proteoglycans is lacking because most approaches use mutant enzymes that regulate glycosaminoglycan biosynthesis, which affects all proteoglycans. At the meeting, Juan Larrain (Pontificia Universidad Católica de Chile, Santiago, Chile) discussed the function of individual proteoglycans during early development of the Xenopus embryo. He showed that biglycan, a chondroitin sulfate proteoglycan, is expressed during the blastula and gastrula stages. Embryological and biochemical experiments indicate that this proteoglycan interacts with bone morphogen protein 4 (BMP4) and chordin, regulating BMP4 signaling (Moreno et al., 2005Moreno M. Muñoz R. Aroca F. Labarca M. Brandan E. Larraín J. Biglycan is a new extracellular component of the Chordin-BMP4 signalling pathway.EMBO J. 2005; 24: 1397-1405Crossref PubMed Scopus (83) Google Scholar). He also reported identification of a specific heparan sulfate proteoglycan that is involved in convergent extension movements and that regulates noncanonical Wnt signaling. The signaling activities of bioactive lipids in developmental processes have received scant attention. Ruth Lehmann (Skirball Institute, New York) and Diana Escalante-Alcalde (Universidad Nacional Autónoma de México, México City, México) presented data revealing the developmental role of proteins regulating production and signaling of bioactive lipids in Drosophila and mouse. In Drosophila, wunen and wunen2 control the survival and migratory behavior of primordial germ cells (Renault et al., 2004Renault A.D. Sigal Y.J. Morris A.J. Lehmann R. Soma-germ line competition for lipid phosphate uptake regulates germ cell migration and survival.Science. 2004; 305: 1963-1966Crossref PubMed Scopus (68) Google Scholar). Escalante-Alcalde described the role of the wunen ortholog, lipid phosphate phosphatase-3 (Lpp3), during early mouse development. She explained that targeted mutation of Lpp3 leads to embryonic lethality, with a complex phenotype characterized by yolk sac and allantois vascular defects (Escalante-Alcalde et al., 2003Escalante-Alcalde D. Hernandez L. Le Stunff H. Maeda R. Lee H.S. Sciorra V.A. Daar I. Spiegel S. Morris A.J. Stewart C.L. The lipid phosphatase LPP3 regulates extra-embryonic vasculogenesis and axis patterning.Development. 2003; 130: 4623-4637Crossref PubMed Scopus (136) Google Scholar). Abnormal signaling through lysophosphatidic acid/sphingosine-1-phosphate receptors could account for these defects. A subset of embryos exhibited abnormal patterning, which may reflect loss of an antagonistic effect of LPP3 on the canonical Wnt/β-catenin signaling pathway. In vitro studies using a catalytically inactive LPP3 mutant indicate that Wnt signaling suppression is at least partly independent of the phosphatase activity, implying the existence of as yet uncharacterized domains with alternative functional activities. At the cellular level, Lpp3 null cells showed alterations in cell movement, suggesting a conserved role for this group of proteins in regulating cell movement during mouse and Drosophila development. Signaling proteins are also important for tissue regeneration as Nadia Rosenthal (European Molecular Biology Laboratory, Monterotondo, Italy) commented. Using a transgenic mouse model, Rosenthal and her colleagues found that expression of a locally acting isoform of insulin-like growth factor I (IGF-I) in skeletal muscle led to a dramatic increase in muscle mass and strength without any of the associated pathologies usually encountered with hormonally acting IGF-I transgenes. When injured, the muscles of these mice regenerated more rapidly, increasing the recruitment of bone marrow cells and augmenting local stem cell reserves (Musaro et al., 2004Musaro A. Giacinti C. Borsellino G. Dobrowolny G. Pelosi L. Coletta M. Cossu G. Bernardi G. Battistini L. Molinaro M. Rosenthal N. Stem cell-mediated muscle regeneration is enhanced by mIGF-1.Proc. Natl. Acad. Sci. USA. 2004; 101: 1206-1210Crossref PubMed Scopus (215) Google Scholar). At the meeting, Rosenthal presented new results on transgenic mice expressing the locally acting IGF-I isoform in the heart. Preliminary studies indicate that the hearts of these mice also may be capable of regeneration. These studies highlight the central role that signaling proteins play in regenerative medicine. Two Latin American students from the Short Course, who study very unique animal models of tissue regeneration, presented their findings. Cintia Niva (National Institute of Agrobiological Sciences, Tsukuba, Japan) presented her molecular studies of Enchytraeus japonensis (Figure 1E), a terrestrial oligochaete that regenerates new individuals from small body fragments in only 4 to 5 days (Myohara, 2004Myohara M. Differential tissue development during embryogenesis and regeneration in an Annelid.Dev. Dyn. 2004; 231: 349-358Crossref PubMed Scopus (31) Google Scholar). Francisco Ramirez (University of Puerto Rico, Rio Piedras, Puerto Rico) presented his work on the molecular biology of gut regeneration in the sea cucumber, Holothuria glaberrima (Figure 1F), after experimentally induced evisceration (Quiñones et al., 2002Quiñones J.L. Rosa R. Ruiz D.L. Garcia-Arraras J.E. Extracellular matrix remodeling and metalloproteinase involvement during intestine regeneration in the sea cucumber Holothuria glaberrima.Dev. Biol. 2002; 250: 181-197Crossref PubMed Scopus (103) Google Scholar, Murray and Garcia-Arraras, 2004Murray G. Garcia-Arraras J.E. Myogenesis during holothurian intestinal regeneration.Cell Tissue Res. 2004; 318: 515-524Crossref PubMed Scopus (39) Google Scholar). The sea cucumber is able to generate a new gut in about 30 days. Another major theme of the meeting was the use of developmental models to investigate organ formation, homeostasis, and the diseases that are caused by defects in organ development. Eric Moss (University of Medicine and Dentistry, New Jersey) presented his work on the developmental timing regulator Lin-28 in the nematode Caenorhabditis elegans. Lin-28 is part of the genetic pathway that controls developmental timing, the succession of events within tissues, and synchrony between tissues in the worm (Slack and Ruvkun, 1997Slack F. Ruvkun G. Temporal pattern formation by heterochronic genes.Annu. Rev. Genet. 1997; 31: 611-634Crossref PubMed Scopus (88) Google Scholar). Moss showed that the Lin-28 gene is conserved in vertebrates, including mouse and human, and that its expression is temporally regulated in tissues in the developing mouse embryo, particularly in epithelia (Moss and Tang, 2003Moss E.G. Tang L. Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites.Dev. Biol. 2003; 258: 432-442Crossref PubMed Scopus (238) Google Scholar, Yang and Moss, 2003Yang D.H. Moss E.G. Temporally regulated expression of Lin-28 in diverse tissues of the developing mouse.Gene Expr. Patterns. 2003; 3: 719-726Crossref PubMed Scopus (137) Google Scholar). The Lin-28 gene of mammals contains microRNA target sites, suggesting that the restricted expression of the protein in developing tissues is under microRNA control. This is consistent with downregulation of Lin-28 by the microRNA lin-4, another developmental timing regulator (Moss and Tang, 2003Moss E.G. Tang L. Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites.Dev. Biol. 2003; 258: 432-442Crossref PubMed Scopus (238) Google Scholar). The extent of microRNA control of tissue differentiation in vertebrate embryos remains to be determined. As Brad Davidson (University of California, Berkeley) explained to meeting delegates, the urochordate Ciona intestinalis is an appealing system with which to model the early events of cardiac development, which are presumably conserved among chordates (Davidson and Levine, 2003Davidson B. Levine M. Evolutionary origins of the vertebrate heart: Specification of the cardiac lineage in Ciona intestinalis.Proc. Natl. Acad. Sci. USA. 2003; 100: 11469-11473Crossref PubMed Scopus (103) Google Scholar). Davidson reported that in Ciona, the Mesp gene, which encodes a basic Helix-Loop-Helix (b-HLH) transcription factor, is crucial for both cell migration and cardiac specification. Targeted expression of a constitutively activated form of Mesp (Mesp-VP16) induced heart specification but blocked migration in transgenic Ciona embryos that later displayed ectopic beating heart tissue in the resorbed tail as juveniles. Conversely, forced expression of a constitutive repressor Mesp (Mesp-WRPW) induced cell migration but blocked cardiac specification. These experiments suggest a model in which Mesp independently activates target genes required for heart specification but also represses one or more inhibitors of cell migration. The exquisite cellular resolution obtained in Davidson’s studies stressed the uniqueness of Ciona as a platform for studies linking development to cell biology, providing an attractive model to study the sequential migration and fusion of cardiac precursor cells. The vertebrate central nervous system (CNS) is one of the most complex organ systems of the body. Although the vertebrate CNS appears bilaterally symmetrical, it has long been known that there are clear asymmetries. Miguel Concha (University of Chile, Santiago, Chile) highlighted the use of comparative analysis as a fundamental approach to unravel the developmental basis of brain asymmetry in vertebrates. Based on earlier studies that established a direct link between genetics and asymmetric morphology in the dorsal diencephalon of zebrafish (Concha et al., 2003Concha M.L. Russell C. Regan J.C. Tawk M. Sidi S. Gilmour D.T. Kapsimali M. Sumoy L. Goldstone K. Amaya E. et al.Local tissue interactions across the dorsal midline of the forebrain establish CNS laterality.Neuron. 2003; 39: 423-438Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar), Concha has explored the conserved and divergent patterns of asymmetric diencephalic morphology in a variety of vertebrate species, including jawless fish (hagfish), medaka fish, lizards, and rodents. His preliminary analysis indicates that although closely related species, such as zebrafish and medaka, share a fundamental developmental pattern of asymmetry, they also show considerable plasticity in specific developmental traits, such as the asymmetric migration of the parapineal organ, an extraretinal tissue capable of photoreception that lies anterior to the pineal gland. Concha is using related species of lizards indigenous to Chile that either have or lack a parapineal organ to serve as “natural experiments” to complement the ablation experiments carried out in zebrafish aimed at determining the role of this intriguing structure in the development of asymmetry. Pablo Wappner and his group (Instituto Leloir, University of Buenos Aires, Argentina) unveiled a genetic mechanism through which oxygen availability can modulate development in Drosophila (Lavista-Llanos et al., 2002Lavista-Llanos S. Centanin L. Irisarri M. Russo D.M. Gleadle J.M. Bocca S.N. Muzzopappa M. Ratcliffe P.J. Wappner P. Control of the hypoxic response in Drosophila melanogaster by the basic Helix-Loop-Helix PAS protein Similar.Mol. Cell. Biol. 2002; 22: 6842-6853Crossref PubMed Scopus (178) Google Scholar). By dissecting the hypoxia-responsive machinery, Wappner and collaborators showed that mutations in the gene encoding the oxygen sensor Fatiga, a prolyl-4-hydroxylase, are lethal in fly larval or pupal stages. In the fruit fly, fatiga loss-of-function mutants display alterations in the development of the tracheal (respiratory) system that are mimicked by exposure to hypoxia or overexpression of Fatiga’s target, the bHLH-PAS transcription factor, Sima, which is the fly ortholog of HIF-1α. Sima mutants are viable in normoxic conditions but die under hypoxic conditions. However, fatiga/sima double homozygous mutants display normal tracheal development and are viable into adulthood, suggesting that a key function of fatiga in development involves downregulation of the HIF-1α/Sima protein. These studies highlight the role of environmental factors in developmental processes. One very important organ system whose developmental biology has received relatively little attention is the lymphatic system. The lymphatic system circulates body fluids and helps the body to defend itself against pathogens. Prox1 is a homeobox gene that is expressed in lymphatic endothelial cells and is required for the development of the lymphatic vasculature (Wigle and Oliver, 1999Wigle J.T. Oliver G. Prox1 function is required for the development of the murine lymphatic system.Cell. 1999; 98: 769-778Abstract Full Text Full Text PDF PubMed Scopus (1141) Google Scholar). Guillermo Oliver (St. Judes Children’s Research Hospital, Memphis, Tennessee) presented data demonstrating that mice with only a single functional allele of Prox1 develop adult-onset obesity due to the abnormal leakage of lymph/chyle from mispatterned and ruptured lymphatic vessels (Harvey et al., 2005Harvey, N.L., Sathish Srinivasan, R., Dillard, M.E., Johnson, N.C., Witte, M.H., Boyd, K., Sleeman, M.W., and Oliver, G. (2005). Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Nat. Genet., in press.Google Scholar). This defect promotes the ectopic accumulation of fat in lymphatic-rich regions. These studies highlight a previously unknown connection between lymphatic system integrity and body weight homeostasis. Both the LASDB meeting and the Short Course revealed that Latin American researchers are innovative contributors to the study of developmental biology. Interest in the discipline in this region has been growing steadily. Expansion of evo-devo as a discipline has renewed interest in species other than the traditional models of development and has enabled local researchers to take advantage of the enormous biodiversity in Latin America. In addition, the strong interest aroused by the potential therapeutic use of stem cells indicates that the establishment of expertise in developmental biology in Latin American countries is not only a desirable goal but also a strategic one.
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