Lens epithelial cells differentiate into lens fibers (LFs) in response to a fibroblast growth factor (FGF) gradient. This cell fate decision requires the transcription factor Prox1, which has been hypothesized to promote cell cycle exit in differentiating LF cells. However, we find that conditional deletion of Prox1 from mouse lenses results in a failure in LF differentiation despite maintenance of normal cell cycle exit. Instead, RNA-seq demonstrated that Prox1 functions as a global regulator of LF cell gene expression. Intriguingly, Prox1 also controls the expression of fibroblast growth factor receptors (FGFRs) and can bind to their promoters, correlating with decreased downstream signaling through MAPK and AKT in Prox1 mutant lenses. Further, culturing rat lens explants in FGF increased their expression of Prox1, and this was attenuated by the addition of inhibitors of MAPK. Together, these results describe a novel feedback loop required for lens differentiation and morphogenesis, whereby Prox1 and FGFR signaling interact to mediate LF differentiation in response to FGF.
Lens fiber cells are highly elongated cells with complex membrane morphologies that are critical for the transparency of the ocular lens. Investigations into the molecular mechanisms underlying lens fiber cell elongation were first reported in the 1960s, however, our understanding of the process is still poor nearly 50 years later. This review summarizes what is currently hypothesized about the regulation of lens fiber cell elongation along with the available experimental evidence, and how this information relates to what is known about the regulation of cell shape/elongation in other cell types, particularly neurons.
Foundational and early university STEM courses are usually taught as large lecture courses. For many students, especially students from marginalized identity groups, a large course can be an impersonal experience that leaves students with a low sense of belonging, negatively impacting academic performance and retention in the discipline. In this paper, we present specific interventions and practices—cultivated through years of intentional iteration by multiple faculty—to build a community of learners that care for one another in a large foundational Biology course. We define our “culture of care” as building and maintaining a class structure and climate that empowers students to form relationships that provide emotional support and meet affective needs. We believe this allows students to persist and succeed in the course, and helps to build an understanding of how course material will lead to achievement of their intrinsic academic and career goals. We believe these interventions and practices leverage the unique benefits of large class sizes, including the diversity of students present and the power of shared positive group experiences. In this paper, we describe key aspects of the current course, including (1) pedagogical choices that help students invest in their learning and focus on key scientific skills, (2) training faculty and undergraduate assistant members of the teaching team to build a community that cares, and (3) designing assignments that focus on well-being and teamwork. Throughout this paper, we hope to provide a template that can be adapted to different disciplines and institutions for designing large lecture courses that are inclusive, engaging, and emotionally supportive.
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