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Journal: Developmental cell


COPI mediates retrograde trafficking from the Golgi to the endoplasmic reticulum (ER) and within the Golgi stack, sorting transmembrane proteins bearing C-terminal KKxx or KxKxx motifs. The structure of KxKxx motifs bound to the N-terminal WD-repeat domain of β'-COP identifies electrostatic contacts between the motif and complementary patches at the center of the β'-COP propeller. An absolute requirement of a two-residue spacing between the terminal carboxylate group and first lysine residue results from interactions of carbonyl groups in the motif backbone with basic side chains of β'-COP. Similar interactions are proposed to mediate binding of KKxx motifs by the homologous α-COP domain. Mutation of key interacting residues in either domain or in their cognate motifs abolishes in vitro binding and results in mistrafficking of dilysine-containing cargo in yeast without compromising cell viability. Flexibility between β'-COP WD-repeat domains and the location of cargo binding have implications for COPI coat assembly.

Concepts: Protein, Cell, Cell membrane, Golgi apparatus, Secretion, Endoplasmic reticulum, Glycosylation, Lysosome


Early retinal progenitor cells (RPCs) in vertebrates produce lineages that vary greatly both in terms of cell number and fate composition, yet how this variability is achieved remains unknown. One possibility is that these RPCs are individually distinct and that each gives rise to a unique lineage. Another is that stochastic mechanisms play upon the determinative machinery of equipotent early RPCs to drive clonal variability. Here we show that a simple model, based on the independent firing of key fate-influencing transcription factors, can quantitatively account for the intrinsic clonal variance in the zebrafish retina and predict the distributions of neuronal cell types in clones where one or more of these fates are made unavailable.

Concepts: DNA, Neuron, Genetics, Cell nucleus, Gene expression, Developmental biology, Retina, Zebrafish


An important feature of the mammary gland is its ability to undergo repeated morphological changes during each reproductive cycle with profound tissue expansion in pregnancy and regression in involution. However, the mechanisms that determine the tissue’s cyclic regenerative capacity remain elusive. We have now discovered that Cre-Lox ablation of Rac1 in mammary epithelia causes gross enlargement of the epithelial tree and defective alveolar regeneration in a second pregnancy. Architectural defects arise because loss of Rac1 disrupts clearance in involution following the first lactation. We show that Rac1 is crucial for mammary alveolar epithelia to switch from secretion to a phagocytic mode and rapidly remove dying neighbors. Moreover, Rac1 restricts the extrusion of dying cells into the lumen, thus promoting their eradication by live phagocytic neighbors while within the epithelium. Without Rac1, residual milk and cell corpses flood the ductal network, causing gross dilation, chronic inflammation, and defective future regeneration.

Concepts: Prolactin, Secretion, Epithelium, Milk, Skin, Progesterone, Gland, Mammary gland


IRE1α, the most conserved transducer of the unfolded protein response, plays critical roles in many biological processes and cell fate decisions. Reporting in Science, Upton et al. (2012) broadened our understanding of IRE1α as a cell-death executioner, showing that upon ER stress, IRE1α degrades microRNAs to promote translation of caspase-2.

Concepts: DNA, Proteins, Gene, Enzyme, Cell biology, Genetic code, Unfolded protein response, Sword


Plant shoots display indeterminate growth, while their evolutionary decedents, the leaves, are determinate. Determinate leaf growth is conditioned by the CIN-TCP transcription factors, which promote leaf maturation and are negatively regulated by miR319 in leaf primordia. Here we show that CIN-TCPs reduce leaf sensitivity to cytokinin (CK), a phytohormone implicated in inhibition of differentiation in the shoot. We identify the SWI/SNF chromatin remodeling ATPase BRAHMA (BRM) as a genetic mediator of CIN-TCP activities and CK responses. An interactome screen further revealed that SWI/SNF complex components including BRM preferentially interacted with basic-helix-loop-helix (bHLH) transcription factors and the bHLH-related CIN-TCPs. Indeed, TCP4 and BRM interacted in planta. Both TCP4 and BRM bound the promoter of an inhibitor of CK responses, ARR16, and induced its expression. Reconstituting ARR16 levels in leaves with reduced CIN-TCP activity restored normal growth. Thus, CIN-TCP and BRM together promote determinate leaf growth by stage-specific modification of CK responses.

Concepts: DNA, Photosynthesis, Genetics, Gene expression, Transcription factor, Activator, Plant morphology, Shoot


Plants undergo alternation of generation in which reproductive cells develop in the plant body (“sporophytic generation”) and then differentiate into a multicellular gamete-forming “gametophytic generation.” Different populations of helper cells assist in this transgenerational journey, with somatic tissues supporting early development and single nurse cells supporting gametogenesis. New data reveal a two-way relationship between early reproductive cells and their helpers involving complex epigenetic and signaling networks determining cell number and fate. Later, the egg cell plays a central role in specifying accessory cells, whereas in both gametophytes, companion cells contribute non-cell-autonomously to the epigenetic landscape of the gamete genomes.

Concepts: Organism, Developmental biology, Reproductive system, Spore, Gamete, Fern, Gametophyte, Sporophyte


Novel developmental programs often evolve via cooption of existing genetic networks. To understand this process, we explored cooption of the TAS3 tasiRNA pathway in the moss Physcomitrella patens. We find an ancestral function for this repeatedly redeployed pathway in the spatial regulation of a conserved set of Auxin Response Factors. In moss, this results in stochastic patterning of the filamentous protonemal tissue. Through modeling and experimentation, we demonstrate that tasiRNA regulation confers sensitivity and robustness onto the auxin response. Increased auxin sensitivity parallels increased developmental sensitivity to nitrogen, a key environmental signal. We propose that the properties lent to the auxin response network, along with the ability to stochastically modulate development in response to environmental cues, have contributed to repeated cooption of the tasiRNA-ARF module during evolution. The signaling properties of a genetic network, and not just its developmental output, are thus critical to understanding evolution of multicellular forms.

Concepts: Gene expression, Bioinformatics, Developmental biology, Cellular differentiation, Moss, Physcomitrella patens, Mosses, Ralf Reski


Recent discoveries of regulated cell death in bacteria have led to speculation about possible benefits that apoptosis-like pathways may confer to single-celled organisms. However, establishing how these pathways provide increased ecological fitness has remained difficult to determine. Here, we report a pathway in Bacillus subtilis in which regulated cell death maintains the fidelity of sporulation through selective removal of cells that misassemble the spore envelope. The spore envelope, which protects the dormant spore’s genome from environmental insults, uses the protein SpoIVA as a scaffold for assembly. We found that disrupting envelope assembly activates a cell death pathway wherein the small protein CmpA acts as an adaptor to the AAA+ ClpXP protease to degrade SpoIVA, thereby halting sporulation and resulting in lysis of defective sporulating cells. We propose that removal of unfit cells from a population of terminally differentiating cells protects against evolutionary deterioration and ultimately loss of the sporulation program.

Concepts: DNA, Gene, Archaea, Bacteria, Metabolism, Organism, Virus, Eukaryote


Novel body structures are often generated by the redeployment of ancestral components of the genome. In this issue of Developmental Cell, Glassford et al. (2015) present a thorough analysis of the co-option of a gene regulatory network in the origin of an evolutionary novelty.

Concepts: DNA, Gene, Genetics, Gene expression, Archaea, Bacteria, Organism, Virus


Skin development requires communication between epithelial and mesenchymal cells, melanocytes, and neurons. In this issue of Developmental Cell, Sennett et al. (2015) shed new light on these mechanisms by simultaneously profiling multiple different cell types in embryonic mouse skin at the onset of hair follicle formation.

Concepts: Protein, Gene, Developmental biology, Stem cell, Cell type, Skin, Epidermis, Hair follicle