597B Poster - 08. Patterning, morphogenesis and organogenesis
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Rajprasad Loganathan ¹; Daniel Levings ²; Ji Hoon Kim ¹; Michael Wells ³; Hannah Chiu ¹; Yifan Wu ¹; Matthew Slattery ²; Deborah Andrew ¹

Affiliations:
1) Johns Hopkins University; 2) University of Minnesota Medical School; 3) Idaho College of Osteopathic Medicine

Keywords:
o. tissue growth and remodeling; h. translational regulation

Developmental tissue growth in the Drosophila embryo has hitherto been ascribed exclusively to the contributions from early mitotic cycles. Post mitotic non-proliferative growth of embryonic tissues has, therefore, been considered negligible for organogenesis. In this work, we describe a significant contribution of non-proliferative cell growth to the formation of two embryonic tubular organs—the salivary gland (SG) and the trachea. The BTB-domain transcription factor Ribbon (Rib) plays a critical role in promoting growth of both organs. In the SG, loss of Rib results in abnormal cell shape and a significant reduction in cell size, attributable to a loss of cytoplasmic volume gain during embryogenesis. In the trachea, Rib loss also results in a significant reduction in cell volume and a failure of segmental branch connectivity. Tissue-specific ChIP-Seq revealed that, in the SG, Rib binds almost all SG-expressed ribosomal protein genes (RPGs). Follow-up transcription assays (RT-qPCR and FISH) revealed that Rib is required for high levels of expression of all ten of the RPGs we have so far tested. Although Rib can directly bind SG RPG enhancers in vitro, the binding is both weak and not sequence selective. We have demonstrated, however, that Rib may attain specificity for RPG enhancer binding and transcriptional activation through direct cooperative interactions with three previously known activators of RPG expression—Trf2, M1BP, and Dref. Rib, in addition to binding SG RPGs, also binds translation factors and chaperones (other components of the “translatome”) implicated in protein synthesis. The mechanism by which Rib-dependent SG cell growth occurs—boosting expression of RPGs and other components of translation—suggests functional consequences beyond cell growth, i.e., priming this organ for its secretory function by enriching the translational machinery to coordinate organ form with function. Surprisingly, Rib binds non-ribosomal genes to promote cell growth in the embryonic trachea where tissue growth is geared primarily to meet the demands of branch connectivity rather than secretion. The differential deployment of cell growth mediators in these two tissues by a single transcription factor suggests a model in which the growth of individual tissues is customized to coordinate organ form with function.