RESUMEN
Organogenesis is a complex process requiring multiple cell types to associate with one another through correct cell contacts and in the correct location to achieve proper organ morphology and function. To better understand the mechanisms underlying gonad formation, we performed a mutagenesis screen in Drosophila and identified twenty-four genes required for gonadogenesis. These genes affect all different aspects of gonad formation and provide a framework for understanding the molecular mechanisms that control these processes. We find that gonad formation is regulated by multiple, independent pathways; some of these regulate the key cell adhesion molecule DE-cadherin, while others act through distinct mechanisms. In addition, we discover that the Slit/Roundabout pathway, best known for its role in regulating axonal guidance, is essential for proper gonad formation. Our findings shed light on the complexities of gonadogenesis and the genetic regulation required for proper organ formation.
Asunto(s)
Proteínas de Drosophila/genética , Drosophila/embriología , Drosophila/genética , Genes de Insecto , Gónadas/embriología , Proteínas del Tejido Nervioso/genética , Receptores Inmunológicos/genética , Animales , Animales Modificados Genéticamente , Cadherinas/genética , Células Madre Embrionarias/citología , Regulación del Desarrollo de la Expresión Génica , Células Germinativas/citología , Gónadas/citología , Mutagénesis , Mutación , Fenotipo , Transducción de Señal , Proteínas RoundaboutRESUMEN
The large funding opportunities created by the US Congress have allowed the military and civilian orthopaedic communities to collaborate to define clinical problems and develop solutions. It is believed that this research effort will be constructive in the short term because of emphasis placed on funding projects that used relevant populations and approaches that will benefit patients soon. The immediate results will define best practice guidelines. Additionally, new therapies will be fielded that will reduce complications and improve the outcomes of both injured service personnel and civilians.
Asunto(s)
Investigación Biomédica/legislación & jurisprudencia , Financiación del Capital/legislación & jurisprudencia , Programas de Gobierno/economía , Ortopedia/economía , Humanos , Estados UnidosRESUMEN
Embryonic gonad formation involves intimate contact between germ cells and specialized somatic cells along with the complex morphogenetic movements necessary to create proper gonad architecture. Previously, we have shown that gonad formation in Drosophila requires the homophilic cell-adhesion molecule Drosophila E-cadherin (DE-cadherin), and also Fear of Intimacy (FOI), which is required for stable accumulation of DE-cadherin protein in the gonad. Here, we present an in vivo structure-function analysis of FOI that strongly indicates that zinc transport activity of FOI is essential for gonad development. Mutant forms of FOI that are defective for zinc transport also fail to rescue morphogenesis and DE-cadherin expression in the gonad. We further show that expression of DE-cadherin in the gonad is regulated post-transcriptionally and that foi affects this post-transcriptional control. Expression of DE-cadherin from a ubiquitous (tubulin) promoter still results in gonad-specific accumulation of DE-cadherin, which is strongly reduced in foi mutants. This work indicates that zinc is a crucial regulator of developmental processes and can affect DE-cadherin expression on multiple levels.
