@article{21015,
  abstract     = {Early embryo geometry is one of the most invariant species-specific traits, yet its role in ensuring developmental reproducibility and robustness remains underexplored. Here we show that in zebrafish, the geometry of the fertilized egg—specifically its curvature and volume—serves as a critical initial condition triggering a cascade of events that influence development. The embryo geometry guides patterned asymmetric cell divisions in the blastoderm, generating radial gradients of cell volume and nucleocytoplasmic ratio. These gradients generate mitotic phase waves, with the nucleocytoplasmic ratio determining individual cell cycle periods independently of other cells. We demonstrate that reducing cell autonomy reshapes these waves, emphasizing the instructive role of geometry-derived volume patterns in setting the intrinsic period of the cell cycle oscillator. In addition to organizing cell cycles, early embryo geometry spatially patterns zygotic genome activation at the midblastula transition, a key step in establishing embryonic autonomy. Disrupting the embryo shape alters the zygotic genome activation pattern and causes ectopic germ layer specification, underscoring the developmental significance of geometry. Together, our findings reveal a symmetry-breaking function of early embryo geometry in coordinating cell cycle and transcriptional patterning.},
  author       = {Mishra, Nikhil and Li, Yuting I and Hannezo, Edouard B and Heisenberg, Carl-Philipp J},
  issn         = {1745-2481},
  journal      = {Nature Physics},
  pages        = {139--150},
  publisher    = {Springer Nature},
  title        = {{Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo}},
  doi          = {10.1038/s41567-025-03122-1},
  volume       = {22},
  year         = {2026},
}

@article{20183,
  abstract     = {The unequal segregation of organelles has been proposed to be an intrinsic mechanism that contributes to cell fate divergence during asymmetric cell division; however, in vivo evidence is sparse. Using super-resolution microscopy, we analysed the segregation of organelles during the division of the neuroblast QL.p in C. elegans larvae. QL.p divides to generate a daughter that survives, QL.pa, and a daughter that dies, QL.pp. We found that mitochondria segregate unequally by density and morphology and that this is dependent on mitochondrial dynamics. Furthermore, we found that mitochondrial density in QL.pp correlates with the time it takes QL.pp to die. We propose that low mitochondrial density in QL.pp promotes the cell death fate and ensures that QL.pp dies in a highly reproducible and timely manner. Our results provide in vivo evidence that the unequal segregation of mitochondria can contribute to cell fate divergence during asymmetric cell division in a developing animal.},
  author       = {Segos, Ioannis and Van Eeckhoven, Jens and Berger, Simon and Mishra, Nikhil and Lambie, Eric J. and Conradt, Barbara},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Unequal segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in sister cells in vivo}},
  doi          = {10.1038/s41467-025-62484-5},
  volume       = {16},
  year         = {2025},
}

@article{17066,
  abstract     = {A cell’s size affects the likelihood that it will die. But how is cell size controlled in this context and how does cell size impact commitment to the cell death fate? We present evidence that the caspase CED-3 interacts with the RhoGEF ECT-2 in Caenorhabditis elegans neuroblasts that generate “unwanted” cells. We propose that this interaction promotes polar actomyosin contractility, which leads to unequal neuroblast division and the generation of a daughter cell that is below the critical “lethal” size threshold. Furthermore, we find that hyperactivation of ECT-2 RhoGEF reduces the sizes of unwanted cells. Importantly, this suppresses the “cell death abnormal” phenotype caused by the partial loss of ced-3 caspase and therefore increases the likelihood that unwanted cells die. A putative null mutation of ced-3 caspase, however, is not suppressed, which indicates that cell size affects CED-3 caspase activation and/or activity. Therefore, we have uncovered novel sequential and reciprocal interactions between the apoptosis pathway and cell size that impact a cell’s commitment to the cell death fate.},
  author       = {Sethi, Aditya and Wei, Hai and Mishra, Nikhil and Segos, Ioannis and Lambie, Eric J. and Zanin, Esther and Conradt, Barbara},
  issn         = {1545-7885},
  journal      = {PLOS Biology},
  number       = {10},
  publisher    = {Public Library of Science},
  title        = {{A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans}},
  doi          = {10.1371/journal.pbio.3001786},
  volume       = {20},
  year         = {2022},
}

@article{10406,
  abstract     = {Multicellular organisms develop complex shapes from much simpler, single-celled zygotes through a process commonly called morphogenesis. Morphogenesis involves an interplay between several factors, ranging from the gene regulatory networks determining cell fate and differentiation to the mechanical processes underlying cell and tissue shape changes. Thus, the study of morphogenesis has historically been based on multidisciplinary approaches at the interface of biology with physics and mathematics. Recent technological advances have further improved our ability to study morphogenesis by bridging the gap between the genetic and biophysical factors through the development of new tools for visualizing, analyzing, and perturbing these factors and their biochemical intermediaries. Here, we review how a combination of genetic, microscopic, biophysical, and biochemical approaches has aided our attempts to understand morphogenesis and discuss potential approaches that may be beneficial to such an inquiry in the future.},
  author       = {Mishra, Nikhil and Heisenberg, Carl-Philipp J},
  issn         = {1545-2948},
  journal      = {Annual Review of Genetics},
  keywords     = {morphogenesis, forward genetics, high-resolution microscopy, biophysics, biochemistry, patterning},
  pages        = {209--233},
  publisher    = {Annual Reviews},
  title        = {{Dissecting organismal morphogenesis by bridging genetics and biophysics}},
  doi          = {10.1146/annurev-genet-071819-103748},
  volume       = {55},
  year         = {2021},
}