Annual Review of Cell and Developmental Biology - Current Issue

Since first identified as a separate domain of life in the 1970s, it has become clear that archaea differ profoundly from both eukaryotes and bacteria. In this review, we look across the archaeal domain and discuss the diverse mechanisms by which archaea control cell cycle progression, DNA replication, and cell division. While the molecular and cellular processes archaea use to govern these critical cell biological processes often differ markedly from those described in bacteria and eukaryotes, there are also striking similarities that highlight both unique and common principles of cell cycle control across the different domains of life. Since much of the eukaryotic cell cycle machinery has its origins in archaea, exploration of the mechanisms of archaeal cell division also promises to illuminate the evolution of the eukaryotic cell cycle.

Life on Earth has been through numerous challenges over eons and, one way or another, has always triumphed. From mass extinctions to more daily plights to find food, unpredictability is everywhere. The adaptability of life-forms to ever-changing environments is the key that confers life's robustness. Adaptability has become synonymous with Darwinian evolution mediated by heritable genetic changes. The extreme gene-centric view, while being of central significance, at times has clouded our appreciation of the cell as a self-regulating entity informed of, and informing, the genetic data. An essential element that powers adaptability is the ability to regulate cell growth. In this review, we provide an extensive overview of growth regulation spanning species, tissues, and regulatory mechanisms. We aim to highlight the commonalities, as well as differences, of these phenomena and their molecular regulators. Finally, we curate open questions and areas for further exploration.

Instances of multicellularity across the tree of life have fostered the evolution of complex organs composed of distinct cell types that cooperate, producing emergent biological functions. How organs originate is a fundamental evolutionary problem that has eluded deep mechanistic and conceptual understanding. Here I propose a cell- to organ-level transitions framework, whereby cooperative division of labor originates and becomes entrenched between cell types through a process of functional niche creation, cell-type subfunctionalization, and irreversible ratcheting of cell interdependencies. Comprehending this transition hinges on explaining how these processes unfold molecularly in evolving populations. Recent single-cell transcriptomic studies and analyses of terminal fate specification indicate that cellular functions are conferred by modular gene expression programs. These discrete components of functional variation may be deployed or combined within cells to introduce new properties into multicellular niches, or partitioned across cells to establish division of labor. Tracing gene expression program evolution at the level of single cells in populations may reveal transitions toward organ complexity.

Embryonic development is a dynamic process orchestrated by a delicate interplay of biochemical and biophysical factors. While the role of genetics and biochemistry in embryogenesis has been extensively studied, recent research has highlighted the significance of mechanical regulation in shaping and guiding this intricate process. Here, we provide an overview of the current understanding of the mechanical regulation of embryo development. We explore how mechanical forces generated by cells and tissues play a crucial role in driving the development of different stages. We examine key morphogenetic processes such as compaction, blastocyst formation, implantation, and egg cylinder formation, and discuss the mechanical mechanisms and cues involved. By synthesizing the current body of literature, we highlight the emerging concepts and open questions in the field of mechanical regulation. We aim to provide an overview of the field, inspiring future investigations and fostering a deeper understanding of the mechanical aspects of embryo development.

Although most animals appear symmetric externally, they exhibit chirality within their body cavity, i.e., in terms of asymmetric organ position, directional organ looping, and lateralized organ function. Left-right (LR) asymmetry is determined genetically by intricate molecular interactions that occur during development. Key genes have been elucidated in several species. There are common mechanisms in vertebrates and invertebrates, but some appear to exhibit unique mechanisms. This review focuses on LR asymmetry formation in invertebrates, particularly Drosophila, ascidians, and mollusks. It aims to understand the role of the genes that are key to creating LR asymmetry and how chirality information is converted/transmitted across the hierarchies from molecules to cells and from cells to tissues.

Developmental biology has greatly profited from genetic and reverse genetic approaches to indirectly studying protein function. More recently, nanobodies and other protein binders derived from different synthetic scaffolds have been used to directly dissect protein function. Protein binders have been fused to functional domains, such as to lead to protein degradation, relocalization, visualization, or posttranslational modification of the target protein upon binding. The use of such functionalized protein binders has allowed the study of the proteome during development in an unprecedented manner. In the coming years, the advent of the computational design of protein binders, together with further advances in scaffold engineering and synthetic biology, will fuel the development of novel protein binder–based technologies. Studying the proteome with increased precision will contribute to a better understanding of the immense molecular complexities hidden in each step along the way to generate form and function during development.

Lipid droplets (LDs) are dynamic storage organelles with central roles in lipid and energy metabolism. They consist of a core of neutral lipids, such as triacylglycerol, which is surrounded by a monolayer of phospholipids and specialized surface proteins. The surface composition determines many of the LD properties, such as size, subcellular distribution, and interaction with partner organelles. Considering the diverse energetic and metabolic demands of various cell types, it is not surprising that LDs are highly heterogeneous within and between cell types. Despite their diversity, all LDs share a common biogenesis mechanism. However, adipocytes have evolved specific adaptations of these basic mechanisms, enabling the regulation of lipid and energy metabolism at both the cellular and organismal levels. Here, we discuss recent advances in the understanding of both the general mechanisms of LD biogenesis and the adipocyte-specific adaptations controlling these fascinating organelles.

Oxygenic photosynthesis evolved billions of years ago, becoming Earth's main source of biologically available carbon and atmospheric oxygen. Since then, phototrophic organisms have diversified from prokaryotic cyanobacteria into several distinct clades of eukaryotic algae and plants through endosymbiosis events. This diversity can be seen in the thylakoid membranes, complex networks of lipids, proteins, and pigments that perform the light-dependent reactions of photosynthesis. In this review, we highlight the structural diversity of thylakoids, following the evolutionary history of phototrophic species. We begin with a molecular inventory of different thylakoid components and then illustrate how these building blocks are integrated to form membrane networks with diverse architectures. We conclude with an outlook on understanding how thylakoids remodel their architecture and molecular organization during dynamic processes such as biogenesis, repair, and environmental adaptation.

The fidelity of genetic information is essential for cellular function and viability. DNA double-strand breaks (DSBs) pose a significant threat to genome integrity, necessitating efficient repair mechanisms. While the predominant repair strategies are usually accurate, paradoxically, error-prone pathways also exist. This review explores recent advances and our understanding of microhomology-mediated end joining (MMEJ), an intrinsically mutagenic DSB repair pathway conserved across organisms. Central to MMEJ is the activity of DNA polymerase theta (Polθ), a specialized polymerase that fuels MMEJ mutagenicity. We examine the molecular intricacies underlying MMEJ activity and discuss its function during mitosis, where the activity of Polθ emerges as a last-ditch effort to resolve persistent DSBs, especially when homologous recombination is compromised. We explore the promising therapeutic applications of targeting Polθ in cancer treatment and genome editing. Lastly, we discuss the evolutionary consequences of MMEJ, highlighting its delicate balance between protecting genome integrity and driving genomic diversity.

Mitochondria serve as energetic and signaling hubs of the cell: This function results from the complex interplay between their structure, function, dynamics, interactions, and molecular organization. The ability to observe and quantify these properties often represents the puzzle piece critical for deciphering the mechanisms behind mitochondrial function and dysfunction. Fluorescence microscopy addresses this critical need and has become increasingly powerful with the advent of superresolution methods and context-sensitive fluorescent probes. In this review, we delve into advanced light microscopy methods and analyses for studying mitochondrial ultrastructure, dynamics, and physiology, and highlight notable discoveries they enabled.

Ribosomes synthesize protein in all cells. Maintaining both the correct number and composition of ribosomes is critical for protein homeostasis. To address this challenge, cells have evolved intricate quality control mechanisms during assembly to ensure that only correctly matured ribosomes are released into the translating pool. However, these assembly-associated quality control mechanisms do not deal with damage that arises during the ribosomes’ exceptionally long lifetimes and might equally compromise their function or lead to reduced ribosome numbers. Recent research has revealed that ribosomes with damaged ribosomal proteins can be repaired by the release of the damaged protein, thereby ensuring ribosome integrity at a fraction of the energetic cost of producing new ribosomes, appropriate for stress conditions. In this article, we cover the types of ribosome damage known so far, and then we review the known repair mechanisms before surveying the literature for possible additional instances of repair.

Antibodies that gain specificity by a large insert encoding for an extra domain were described for the first time in 2016. In malaria-exposed individuals, an exon deriving from the leukocyte-associated immunoglobulin-like 1 (LAIR1) gene integrated via a copy-and-paste insertion into the immunoglobulin heavy chain encoding region. A few years later, a second example was identified, namely a dual exon integration from the leukocyte immunoglobulin-like receptor B1 (LILRB1) gene that is located in close proximity to LAIR1. A dedicated high-throughput characterization of chimeric immunoglobulin heavy chain transcripts unraveled, that insertions from distant genomic regions (including mitochondrial DNA) can contribute to human antibody diversity. This review describes the modalities of insert-containing antibodies. The role of known DNA mobility aspects, such as genomic translocation, gene conversion, and DNA fragility, is discussed in the context of insert-antibody generation. Finally, the review covers why insert antibodies were omitted from the past repertoire analyses and how insert antibodies can contribute to protective immunity or an autoreactive response.

Medullary thymic epithelial cells (mTECs) generate immunological self-tolerance by ectopically expressing peripheral-tissue antigens (PTAs) within the thymus to preview the peripheral self to maturing T cells. Recent work, drawing inspiration from old histological observations, has shown that subtypes of mTECs, collectively termed mimetic cells, co-opt developmental programs from throughout the organism to express biologically coherent groups of PTAs. Here, we review key aspects of mimetic cells, especially as they relate to the larger contexts of molecular, cellular, developmental, and evolutionary biology. We highlight lineage-defining transcription factors as key regulators of mimetic cells and speculate as to what other factors, including Aire and the chromatin potential of mTECs, permit mimetic cell differentiation and function. Last, we consider what mimetic cells can teach us about not only the thymus but also other tissues.

One of the fundamental questions in developmental biology is how a cell is specified to differentiate as a specialized cell type. Traditionally, plant cell types were defined based on their function, location, morphology, and lineage. Currently, in the age of single-cell biology, researchers typically attempt to assign plant cells to cell types by clustering them based on their transcriptomes. However, because cells are dynamic entities that progress through the cell cycle and respond to signals, the transcriptome also reflects the state of the cell at a particular moment in time, raising questions about how to define a cell type. We suggest that these complexities and dynamics of cell states are of interest and further consider the roles signaling, stochasticity, cell cycle, and mechanical forces play in plant cell fate specification. Once established, cell identity must also be maintained. With the wealth of single-cell data coming out, the field is poised to elucidate both the complexity and dynamics of cell states.

Expansins comprise an ancient group of cell wall proteins ubiquitous in land plants and their algal ancestors. During cell growth, they facilitate passive yielding of the wall's cellulose networks to turgor-generated tensile stresses, without evidence of enzymatic activity. Expansins are also implicated in fruit softening and other developmental processes and in adaptive responses to environmental stresses and pathogens. The major expansin families in plants include α-expansins (EXPAs), which act on cellulose-cellulose junctions, and β-expansins, which can act on xylans. EXPAs mediate acid growth, which contributes to wall enlargement by auxin and other growth agents. The genomes of diverse microbes, including many plant pathogens, also encode expansins designated expansin-like X. Expansins are proposed to disrupt noncovalent bonding between laterally aligned polysaccharides (notably cellulose), facilitating wall loosening for a variety of biological roles.

Sensory receptors are at the interface between an organism and its environment and thus represent key sites for biological innovation. Here, we survey major sensory receptor families to uncover emerging evolutionary patterns. Receptors for touch, temperature, and light constitute part of the ancestral sensory toolkit of animals, often predating the evolution of multicellularity and the nervous system. In contrast, chemoreceptors exhibit a dynamic history of lineage-specific expansions and contractions correlated with the disparate complexity of chemical environments. A recurring theme includes independent transitions from neurotransmitter receptors to sensory receptors of diverse stimuli from the outside world. We then provide an overview of the evolutionary mechanisms underlying sensory receptor diversification and highlight examples where signatures of natural selection are used to identify novel sensory adaptations. Finally, we discuss sensory receptors as evolutionary hotspots driving reproductive isolation and speciation, thereby contributing to the stunning diversity of animals.

Neural stem cells (NSCs) persist in the adult mammalian brain and are able to give rise to new neurons and glia throughout life. The largest stem cell niche in the adult mouse brain is the ventricular-subventricular zone (V-SVZ) lining the lateral ventricles. Adult NSCs in the V-SVZ coexist in quiescent and actively proliferating states, and they exhibit a regionalized molecular identity. The importance of such spatial diversity is just emerging, as depending on their position within the niche, adult NSCs give rise to distinct subtypes of olfactory bulb interneurons and different types of glia. However, the functional relevance of stem cell heterogeneity in the V-SVZ is still poorly understood. Here, we put into perspective findings highlighting the importance of adult NSC diversity for brain plasticity, and how the body signals to brain stem cells in different physiological states to regulate their behavior.

In animals, the nervous system evolved as the primary interface between multicellular organisms and the environment. As organisms became larger and more complex, the primary functions of the nervous system expanded to include the modulation and coordination of individual responsive cells via paracrine and synaptic functions as well as to monitor and maintain the organism's own internal environment. This was initially accomplished via paracrine signaling and eventually through the assembly of multicell circuits in some lineages. Cells with similar functions and centralized nervous systems have independently arisen in several lineages. We highlight the molecular mechanisms that underlie parallel diversifications of the nervous system.

“What makes us human?” is a central question of many research fields, notably anthropology. In this review, we focus on the development of the human neocortex, the part of the brain with a key role in cognition, to gain neurobiological insight toward answering this question. We first discuss cortical stem and progenitor cells and human-specific genes that affect their behavior. We thus aim to understand the molecular foundation of the expansion of the neocortex that occurred in the course of human evolution, as this expansion is generally thought to provide a basis for our unique cognitive abilities. We then review the emerging evidence pointing to differences in the development of the neocortex between present-day humans and Neanderthals, our closest relatives. Finally, we discuss human-specific genes that have been implicated in neuronal circuitry and offer a perspective for future studies addressing the question of what makes us human.