Characterization of Two G-Protein Coupled Receptors and One Fox Transcription Factor in Drosophila Embryonic Development

Drosophila;salivary gland;GPCR;migration;not listed

Hanlon, Caitlin D.Corden, Jeffry L. ;

Johns Hopkins University

关键词: Drosophila;    salivary gland;    GPCR;    migration;    not listed;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/40207/HANLON-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Cell migration is an exquisitely intricate process common to many higher organisms.Variations in the signals driving cell movement, the distance cells travel, and whether cells migrate as individuals, clusters, or as intact epithelia are all possible. Cell migration can be beneficial, as in development or wound healing, or detrimental, as in cancer metastasis. To begin to unravel the complexities inherent to cell migration, the Andrew lab uses the Drosophila salivary gland as a relatively simple model system for learning the molecular/cellular events underlying cell movement. The salivary gland begins as a placode of polarized columnar epithelial cells on the surface of the embryo that invaginates and move dorsally until a turning point is reached. There, it reorients and begins posterior migration, which continues until the gland reaches its final position along the anterior-posterior axis of the embryo. The broad goal of my work is to identify and characterize other key players in salivary gland migration.I characterized two G-protein coupled receptors (GPCRs) – Tre1 and mthl5 – which are expressed dynamically in the embryo. By creating a null allele of Tre1, I found that Tre1 plays a key role in germ cell migration and affects microtubule organization in the migrating salivary gland. I created a mthl5 mutant allele using the CRISPR/Cas9 system. mthl5 plays a role in the cell shape changes that drive salivary gland invagination.I have identified a potential ligand of Mthl5, fog, which plays a known role in mediating cell shape changes. Mutant alleles of fog phenocopy mutant alleles of mthl5. In a separate project, I characterized the role of the Fox transcription factor FoxL1 in the Drosophila embryo. Mis-expression of FoxL1 causes severe defects in salivary gland migration and muscle organization. I found that FoxL1 is upstream of the signaling molecule sema2a and plan to identify more targets through microarray analysis. Together, these data provide important information for how tissues integrate signaling information to arrive at the correct final destination.