Drosophila T-Box Transcription Factor Midline Functions in the Notch-Delta Signaling Pathway to Regulate Sensory Organ Precursor Cell Fate and Cell Survival and Embryonic Development Profile of Midline, Senseless, and Achaete in the CNS and PNS
Date of Award
Honors College Thesis
Sandra Leal, Ph.D.
The gene mid of Drosophila is a highly conserved gene that codes for a T-box transcription factor with similar functionality to its vertebrate homolog Tbx20. Mid and Tbx20 are important for their roles in heart and CNS development. Additionally, these transcription factors aid in proper eye development but this area of research is vastly understudied. This study uses the eye of Drosophila to report that mid and its paralog H15 expression aid in the specification of sensory organ precursor (SOP) cell fates and cell survival in the pupal eye imaginal disc. Using RNAi interference to reduce mid expression resulted in the loss of interommatidial bristles as well as cell death due to the misspecification of SOP cells during pupal development. We completed genetic studies to place mid in the Notch-Delta genetic pathway because it is known to specify SOP cell fates and were able to determine that Mid functions downstream of Notch, upstream of the Enhancer of Split (E(Spl)) gene complex, and tentatively parallel with Suppressor of Hairless (Su(H)) in the pathway. Additionally, mid interactions with extramacrochaete (emc) and Senseless (sens) play a role in cell survival. These studies suggest that Mid functions within the Notch-Delta signaling pathway with a dual role of cell-fate specification and cell survival.
Another aspect of this research study was to evaluate the role of Mid in the developing central nervous system (CNS) and peripheral nervous system (PNS) of Drosophila embryos. Mid expression was compared to the expression of Sens and Achaete (Ac), SOP cell markers during various stages of embryonic development. Our results show a coordinated co-expression pattern of Sens and Ac with Mid. Sens is highly expressed in the PNS of stages prior to stage 12 and then fades. Ac is expressed in the neurons of the CNS and PNS in early stages and continues after stage 12, which is when Mid expression begins. Ac is co-expressed with Mid beginning in stage 12. Further experiments will be performed using mid-RNAi embryos to evaluate if reducing mid expression affects the expression patterns of Sens and Ac.
This research has clinical applications to further the understanding of developmental and neurodegenerative diseases of the CNS, PNS, and eye. Additionally, Mid may have a link to the development of cancer, an area of research that will be studied in the Leal lab in the future.
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Saucier, Joseph D., "Drosophila T-Box Transcription Factor Midline Functions in the Notch-Delta Signaling Pathway to Regulate Sensory Organ Precursor Cell Fate and Cell Survival and Embryonic Development Profile of Midline, Senseless, and Achaete in the CNS and PNS" (2013). Honors Theses. 140.