@article{21983, abstract = {Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an individual TF binds arbitrary DNA sequences and how individual binding events on the CRE combine to affect gene expression. These insights can be synthesized into a global, biophysically realistic, and quantitative genotype–phenotype map for gene regulation, a ‘holy grail’ for the application of evolutionary theory. A global map provides a rare opportunity to simulate the long-term evolution of regulatory sequences and pose several fundamental questions: How long does it take to evolve CREs de novo? How many non-trivial regulatory functions exist in sequence space? How connected are they? For which regulatory architecture is CRE evolution most rapid and evolvable? In this article, the first of a two-part series, we briefly review the pertinent modeling and simulation efforts for a unique system that enables close, quantitative, and mechanistic links between biophysics, as well as systems, synthetic, and evolutionary biology.}, author = {Mascolo, Elia and Körei, Reka E and Herrera-Álvarez, Santiago and Guet, Calin C and Crocker, Justin and Tkačik, Gašper}, issn = {1879-0380}, journal = {Current Opinion in Genetics & Development}, publisher = {Elsevier}, title = {{Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps}}, doi = {10.1016/j.gde.2026.102483}, volume = {99}, year = {2026}, } @article{21759, abstract = {Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an individual TF binds arbitrary DNA sequences and how individual binding events on the CRE combine to affect gene expression. These insights can be synthesized into a global, biophysically realistic, and quantitative genotype-phenotype (GP) map for gene regulation, a ‘holy grail’ for the application of evolutionary theory. A global map provides a rare opportunity to simulate the long-term evolution of regulatory sequences and pose several fundamental questions: How long does it take to evolve CREs de novo? How many non-trivial regulatory functions exist in sequence space? How connected are they? For which regulatory architecture is CRE evolution most rapid and evolvable? In this article, the second of a two-part series, we review the application of evolutionary concepts — epistasis, robustness, evolvability, tunability, plasticity, and bet-hedging — to the evolution of gene regulatory sequences. We then evaluate the potential for a unifying theory for the evolution of regulatory sequences and identify key open challenges.}, author = {Mascolo, Elia and Körei, Reka E and Borst, Noa O. and Barton, Nicholas H and Crocker, Justin and Tkačik, Gašper}, issn = {1879-0380}, journal = {Current Opinion in Genetics & Development}, publisher = {Elsevier}, title = {{Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges}}, doi = {10.1016/j.gde.2026.102472}, volume = {98}, year = {2026}, } @article{21948, abstract = {The cerebral cortex comprises diverse neuron and glial cell types generated by radial glial progenitors (RGPs) during development. Although RGPs broadly differentiate according to temporally and spatially regulated molecular logics, the lineage hierarchies linking individual progenitors to defined cell (sub)types are not well understood. Clone-resolved transcriptomics, combining molecular barcoding and single-cell RNA sequencing, allow high-resolution lineage tracing at the single-clone/cell level across different species and models. In this mini-review, we synthesize recent advances in this field, uncovering unexpected lineage relationships in the developing brain, with a particular focus on the cerebral cortex. We further highlight new insights into species-specific differences in the developmental programs generating cell-type diversity, linking changes in clonal architecture to lineage diversification during cortical evolution.}, author = {Varela Martínez, Irene and Pipicelli, Fabrizia and Hippenmeyer, Simon}, issn = {1879-0380}, journal = {Current Opinion in Genetics & Development}, publisher = {Elsevier}, title = {{Tracing cell lineages in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics}}, doi = {10.1016/j.gde.2026.102487}, volume = {99}, year = {2026}, } @article{13965, abstract = {Many modes and mechanisms of epigenetic inheritance have been elucidated in eukaryotes. Most of them are relatively short-term, generally not exceeding one or a few organismal generations. However, emerging evidence indicates that one mechanism, cytosine DNA methylation, can mediate epigenetic inheritance over much longer timescales, which are mostly or completely inaccessible in the laboratory. Here we discuss the evidence for, and mechanisms and implications of, such long-term epigenetic inheritance. We argue that compelling evidence supports the long-term epigenetic inheritance of gene body methylation, at least in the model angiosperm Arabidopsis thaliana, and that variation in such methylation can therefore serve as an epigenetic basis for phenotypic variation in natural populations.}, author = {Hollwey, Elizabeth and Briffa, Amy and Howard, Martin and Zilberman, Daniel}, issn = {1879-0380}, journal = {Current Opinion in Genetics & Development}, number = {8}, publisher = {Elsevier}, title = {{Concepts, mechanisms and implications of long-term epigenetic inheritance}}, doi = {10.1016/j.gde.2023.102087}, volume = {81}, year = {2023}, } @article{8131, abstract = {The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes.}, author = {Basilico, Bernadette and Morandell, Jasmin and Novarino, Gaia}, issn = {1879-0380}, journal = {Current Opinion in Genetics & Development}, number = {12}, pages = {126--137}, publisher = {Elsevier}, title = {{Molecular mechanisms for targeted ASD treatments}}, doi = {10.1016/j.gde.2020.06.004}, volume = {65}, year = {2020}, } @article{1004, abstract = {The fundamental tasks of the root system are, besides anchoring, mediating interactions between plant and soil and providing the plant with water and nutrients. The architecture of the root system is controlled by endogenous mechanisms that constantly integrate environmental signals, such as availability of nutrients and water. Extremely important for efficient soil exploitation and survival under less favorable conditions is the developmental flexibility of the root system that is largely determined by its postembryonic branching capacity. Modulation of initiation and outgrowth of lateral roots provides roots with an exceptional plasticity, allows optimal adjustment to underground heterogeneity, and enables effective soil exploitation and use of resources. Here we discuss recent advances in understanding the molecular mechanisms that shape the plant root system and integrate external cues to adapt to the changing environment.}, author = {Ötvös, Krisztina and Benková, Eva}, issn = {0959-437X}, journal = {Current Opinion in Genetics & Development}, pages = {82 -- 89}, publisher = {Elsevier}, title = {{Spatiotemporal mechanisms of root branching}}, doi = {10.1016/j.gde.2017.03.010}, volume = {45}, year = {2017}, } @article{9528, abstract = {Accumulating evidence points toward diverse functions for plant chromatin. Remarkable progress has been made over the last few years in elucidating the mechanisms for a number of these functions. Activity of the histone demethylase IBM1 accurately targets DNA methylation to silent repeats and transposable elements, not to genes. A genetic screen uncovered the surprising role of H2A.Z-containing nucleosomes in sensing precise differences in ambient temperature and consequent gene regulation. Precise maintenance of chromosome number is assured by a histone modification that suppresses inappropriate DNA replication and by centromeric histone H3 regulation of chromosome segregation. Histones and noncoding RNAs regulate FLOWERING LOCUS C, the expression of which quantitatively measures the duration of cold exposure, functioning as memory of winter. These findings are a testament to the power of using plants to research chromatin organization, and demonstrate examples of how chromatin functions to achieve biological accuracy, precision, and memory.}, author = {Huff, Jason T. and Zilberman, Daniel}, issn = {0959-437X}, journal = {Current Opinion in Genetics and Development}, number = {2}, pages = {132--138}, publisher = {Elsevier}, title = {{Regulation of biological accuracy, precision, and memory by plant chromatin organization}}, doi = {10.1016/j.gde.2012.01.007}, volume = {22}, year = {2012}, } @article{4198, abstract = {Animal body plan arises during gastrulation and organogenesis by the coordination of inductive events and cell movements. Several signaling pathways, such as BMP, FGF, Hedgehog, Nodal, and Wnt have well-recognized instructive roles in cell fate specification during vertebrate embryogenesis. Growing evidence indicates that BMP, Nodal, and FGF signaling also regulate cell movements, and that they do so through mechanisms distinct from those that specify cell fates. Moreover, pathways controlling cell movements can also indirectly influence cell fate specification by regulating dimensions and relative positions of interacting tissues. The current challenge is to delineate the molecular mechanisms via which the major signaling pathways regulate cell fate specification and movements, and how these two processes are coordinated to ensure normal development.}, author = {Heisenberg, Carl-Philipp J and Solnica Krezel, Lilianna}, issn = {1879-0380}, journal = {Current Opinion in Genetics & Development}, number = {4}, pages = {311 -- 316}, publisher = {Elsevier}, title = {{Back and forth between cell fate specification and movement during vertebrate gastrulation}}, doi = {10.1016/j.gde.2008.07.011}, volume = {18}, year = {2008}, } @article{9529, abstract = {Eukaryotic organisms have the remarkable ability to inherit states of gene activity without altering the underlying DNA sequence. This epigenetic inheritance can persist over thousands of years, providing an alternative to genetic mutations as a substrate for natural selection. Epigenetic inheritance might be propagated by differences in DNA methylation, post-translational histone modifications, and deposition of histone variants. Mounting evidence also indicates that small interfering RNA (siRNA)-mediated mechanisms play central roles in setting up and maintaining states of gene activity. Much of the epigenetic machinery of many organisms, including Arabidopsis, appears to be directed at silencing viruses and transposable elements, with epigenetic regulation of endogenous genes being mostly derived from such processes.}, author = {Zilberman, Daniel and Henikoff, Steven}, issn = {0959-437X}, journal = {Current Opinion in Genetics and Development}, number = {5}, pages = {557--562}, publisher = {Elsevier}, title = {{Epigenetic inheritance in Arabidopsis: Selective silence}}, doi = {10.1016/j.gde.2005.07.002}, volume = {15}, year = {2005}, }