Activity-Regulated microRNAs: Modulators of Synaptic Growth at the Drosophila Neuromuscular Junction

It is well established that long-term changes in synaptic structure and function are mediated by rapid activity-dependent gene transcription and new protein synthesis. A growing body of evidence supports the involvement of the microRNA (miRNA) pathway in these processes. We have used the Drosophila neuromuscular junction (NMJ) as a model synapse to characterize activity-regulated miRNAs and their important mRNA targets. Here, we have identified five neuronal miRNAs (miRs-1, -8, -289, -314, and -958) that are significantly downregulated in response to neuronal activity. Furthermore we have discovered that neuronal misexpression of three of these miRNAs (miR-8, -289, and -958) is capable of suppressing new synaptic growth in response to activity suggesting that these miRNAs control the translation of biologically relevant target mRNAs. Putative targets of the activity-regulated miRNAs-8 and -289 are significantly enriched in clusters mapping to functional processes including axon development, pathfinding, and axon growth. We demonstrate that activity-regulated miR-8 regulates the 3'UTR of wingless, a presynaptic regulatory protein involved in the process of activity-dependent axon terminal growth. Additionally, we show that the 3'UTR of the protein tyrosine phosophatase leukocyte antengen related (lar), a protein required for axon guidance and synaptic growth, is regulated by activity-regulated miRNAs-8, -289, and -958 in vitro. Both wg and lar were identified as relevant putative targets for co-regulation based through our functional cluster analysis. One putative target of miR-289 is the Ca2+/calmodulin-dependent protein kinase II (CamKII). While CamKII is not predicted as a target for co-regulation by multiple activity-regulated miRNAs we identified it as an especially pertinent target for analysis in our system for two reasons. First, CamKII has an extremely well characterized role in postsynaptic plasticity, but its presynaptic role is less well characterized and bears further analysis. Second, local translation of CamKII mRNA is regulated in part by the miRNA pathway in an activity-dependent manner in dendrites. We find that the CamKII 3'UTR is regulated by miR-289 in-vitro and this regulation is alleviated by mutating the `seed region' of the miR-289 binding site within the CamKII 3'UTR. Furthermore, we demonstrate a requirement for local translation of CamKII in motoneurons in the process of activity-regulated axon terminal growth.

Restrictive and Expansive Views of Equality: A Grounded Theory Study that Explores the Influence of Racial Consciousness on the Behaviors of White Faculty in the Classroom

Attempts to address the ever increasing achievement gap among students have failed to explain how and why educational traditions and teaching practices perpetuate the devaluing of some and the overvaluing of others. This predicament, which plagues our educational system, has been of increased concern, given the growing racial diversity among college students and the saturation of White faculty in the academy. White faculty make up the majority, 79%, of all faculty in the academy. White faculty, whether consciously or unconsciously, are less likely to interrogate how race and racism both privilege them within the academy and influence their faculty behaviors. The result of this cyclical, highly cemented process suggests that there is a relationship between racial consciousness and White faculty members' ability to employ behaviors in their classroom that promote equitable educational outcomes for racially minoritized students. An investigation of the literature revealed that racial consciousness and the behaviors of White faculty in the classroom appeared to be inextricably linked. A conceptual framework, Racial Consciousness and Its Influence on the Behaviors of White Faculty in the Classroom was developed by the author and tested in this study. Constructivist grounded theory was used to explore the role White faculty believe they play in the dismantling of the white supremacy embedded in their classrooms through their faculty behaviors. A substantive theory subsequently emerged. Findings indicate that White faculty with a higher level of racial consciousness employ behaviors in their classroom reflective of a more expansive view of equality in their pursuit of social justice, which they consider synonymous with excellence in teaching. This research bears great significance to higher education research and practice, as it is the first of its kind to utilize critical legal scholar Kimberlé Crenshaw's (1988) restrictive and expansive views of equality framework to empirically measure and describe excellence in college teaching. Implications for faculty preparation and continued education are also discussed.