Organogenesis is a complex process, requiring cells to find their correct location and associate with other cells to achieve the proper morphology of a given organ. To understand these events, we used the Drosophila embryonic gonad as our model system, and performed a mutagenesis screen to identify cellular mechanisms underlying gonad formation. The Drosophila gonad is composed of two cell types, germ cells, and somatic gonadal precursors (SGPs), which must find each other and cooperate to form a gonad. The screen found twenty-four genes, twenty-two previously unknown, that when mutated, result in gonad malformations. Thus, we have increased the number of known factors involved in gonadogenesis by almost six-fold.
The genes can be divided into seven phenotypic categories, based on the extent of gonad formation. Phenotypes are not caused by secondary effects such as early embryonic lethality, incorrect specification of SGPs, or overall mesodermal disruptions (with a few exceptions), but rather due to disruptions that directly affect the gonad. As a whole, the screen revealed that gonad formation is the culmination of many cellular events, some previously unappreciated. Data suggests these events are controlled by multiple overlapping genetic pathways. For example, though all previously known genes involved in gonad formation disrupted DEcad, we found both DEcad dependent and independent genetic pathways.
Each individual gene found in the screen offers new insights into the mechanisms of gonadogenesis. Assays revealed many hints toward the probable function of each gene within the gonad, and similarities in phenotypes often link genes into potential pathways. In addition, genes that have been mapped to a known locus reveal new roles for several signaling cascades in mediating gonad formation, including MAPK, JNK, HH, and surprisingly, the Slit/Robo pathway, as well as several related factors for each path. Together, the pathways and their related factors cooperate throughout gonad development to form and shape the organ. The involvement of these pathways also implicates several other genes in gonad formation. Thus, the screen and the genes it found vastly increases the knowledge base of gonad formation, and provides insight into several cellular and mechanistic events occurring during organogenesis.
|Advisor:||Doren, Mark Van|
|School:||The Johns Hopkins University|
|School Location:||United States -- Maryland|
|Source:||DAI-B 70/05, Dissertation Abstracts International|
|Subjects:||Molecular biology, Genetics|
|Keywords:||Cell migration, Development, Drosophila, Gonadogenesis, Morphogenesis, Organogenesis|
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