The size of nearly all cells is modulated by nutrients. Thus, cells growing in poor nutrients can be nearly half the size of cells in rich nutrients. In budding yeast, cell size is thought to be controlled almost entirely by a mechanism that delays cell cycle entry until sufficient growth has occurred in G1 phase. Here, we show that most growth of a new daughter cell occurs in mitosis. When the rate of growth is slowed by poor nutrients, the duration of mitosis is increased, which suggests that cells compensate for slow growth in mitosis by increasing the duration of growth. The amount of growth required to complete mitosis is reduced in poor nutrients, leading to a large reduction in cell size. Together, these observations suggest that mechanisms that control the extent of growth in mitosis play a major role in cell size control in budding yeast.

Birth defects are among the leading causes of infant mortality and contribute substantially to illness and long-term disability. Defects in Bone Morphogenetic Protein (BMP) signaling are associated with cleft lip/palate. Many craniofacial syndromes are caused by defects in signaling pathways that pattern the cranial neural crest cells (CNCCs) along the dorsal-ventral axis. For example, auriculocondylar syndrome is caused by impaired Endothelin-1 (Edn1) signaling, and Alagille syndrome is caused by defects in Jagged-Notch signaling. The BMP, Edn1, and Jag1b pathways intersect because BMP signaling is required for ventral edn1 expression that, in turn, restricts jag1b to dorsal CNCC territory. In zebrafish, the scaffolding protein Wdr68 is required for edn1 expression and subsequent formation of the ventral Meckel’s cartilage as well as the dorsal Palatoquadrate. Here we report that wdr68 activity is required between the 17-somites and prim-5 stages, that edn1 functions downstream of wdr68, and that wdr68 activity restricts jag1b, hey1, and grem2 expression from ventral CNCC territory. Expression of dlx1a and dlx2a was also severely reduced in anterior dorsal and ventral 1st arch CNCC territory in wdr68 mutants. We also found that the BMP agonist isoliquiritigenin (ISL) can partially rescue lower jaw formation and edn1 expression in wdr68 mutants. However, we found no significant defects in BMP reporter induction or pSmad1/5 accumulation in wdr68 mutant cells or zebrafish. The Transforming Growth Factor Beta (TGF-β) signaling pathway is also known to be important for craniofacial development and can interfere with BMP signaling. Here we further report that TGF-β interference with BMP signaling was greater in wdr68 mutant cells relative to control cells. To determine whether interference might also act in vivo, we treated wdr68 mutant zebrafish embryos with the TGF-β signaling inhibitor SB431542 and found partial rescue of edn1 expression and craniofacial development. While ISL treatment failed, SB431542 partially rescued dlx2a expression in wdr68 mutants. Together these findings reveal an indirect role for Wdr68 in the BMP-Edn1-Jag1b signaling hierarchy and dorso-anterior expression of dlx1a/2a.

Cell size is proportional to growth rate. Thus, cells growing rapidly in rich nutrients can be nearly twice the size of cells growing slowly in poor nutrients. This proportional relationship appears to hold across all orders of life, yet the underlying mechanisms are unknown. In budding yeast, most growth occurs during mitosis, and the proportional relationship between cell size and growth rate is therefore enforced primarily by modulating growth in mitosis. When growth is slow, the duration of mitosis is increased to allow more time for growth, yet the amount of growth required to complete mitosis is reduced, which leads to the birth of small daughter cells. Previous studies have found that Rts1, a member of the conserved B56 family of protein phosphatase 2A regulatory subunits, works in a TORC2 signaling network that influences cell size and growth rate. However, it was unclear whether Rts1 influences cell growth and size in mitosis. Here, we show that Rts1 is required for the proportional relationship between cell size and growth rate during mitosis. Moreover, nutrients and Rts1 influence the duration and extent of growth in mitosis via Wee1 and Pds1/securin, two conserved regulators of mitotic progression. Together, the data are consistent with a model in which global signals that set growth rate also set the critical amount of growth required for cell cycle progression, which would provide a simple mechanistic explanation for the proportional relationship between cell size and growth rate.

Detailed background information, student procedures, sample questions, and instructor's notes, including drawings for fabricating the sample cells and a discussion of two component phase diagrams, are available in this issue of JCE Online.

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A key part of keeping doctoral and postdoctoral trainees in STEM research careers is mentoring. Our previous research indicates that mentoring trainees in scientific communication (SC) skill development increases research career intention through two social-cognitive constructs, self-efficacy in and outcome expectations for acquiring SC skills, as well as science identity. While many mentor training interventions exist, no programs focus on developing SC skills specifically. The “Scientific Communication Advances Research Excellence” (SCOARE) program trains mentors to address trainee scientific communication (SC) skill development as an innovative approach to increase trainee research career persistence. The SCOARE training is a half-day workshop for faculty mentors of research trainees at five sites nationally. Informed by previous research, workshop content focuses on practical, effective mentoring strategies to develop trainee speaking and writing skills. Anonymous evaluation data collected after each workshop indicates participant satisfaction and reported positive increases in skills and knowledge in applying new and various techniques when mentoring trainees (skills) and how linguistic bias influences our perception of others (knowledge). This article outlines the research-based development of the SCOARE program, the first two years’ of workshop evaluations showing positive increases in skills and knowledge, and lessons learned to increase participant satisfaction with the program.

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Cell size is proportional to growth rate. Thus, cells growing slowly in poor nutrients can be nearly half the size of cells growing rapidly in rich nutrients. The relationship between cell size and growth rate appears to hold across all orders of life, yet the underlying mechanisms are unknown. In budding yeast, most growth occurs during mitosis, and the proportional relationship between cell size and growth rate is therefore enforced primarily by modulating growth in mitosis. When growth is slow, the duration of mitosis is increased to allow more time for growth, yet the amount of growth required to complete mitosis is reduced, leading to birth of small daughter cells. Previous studies found that PP2A associated with the Rts1 regulatory subunit (PP2A Rts1 ) works in a TORC2-dependent feedback loop that sets cell size and growth rate to match nutrient availability. However, it was unknown whether PP2A Rts1 influences growth in mitosis. Here, we show that PP2ARts1 is required for the proportional relationship between cell size and growth rate during mitosis. Moreover, nutrients and PP2ARts1 influence the duration of mitosis, and thus the extent of growth in mitosis, via Wee1 and Pds1/securin, two conserved regulators of mitotic progression. Together, the data suggest a model in which the same global signals that set growth rate also set the critical amount of growth required for cell cycle progression, which would provide a simple mechanistic explanation for the proportional relationship between size and growth rate.