Retinoic Acid-Mediated Control of Energy Metabolism Is Essential for Lung Branching Morphogenesis.

Lung branching morphogenesis relies on intricate epithelial-mesenchymal interactions and signaling networks. Still, the interplay between signaling and energy metabolism in shaping embryonic lung development remains unexplored. Retinoic acid (RA) signaling influences lung proximal-distal patterning and branching morphogenesis, but its role as a metabolic modulator is unknown.

Opposing effects of ecdysone signaling regulate neuroblast proliferation to ensure coordination of brain and organism development.

Growth regulation must be robust to ensure correct final size, but also adaptative to adjust to less favorable environmental conditions. Developmental coordination between whole-organism and the brain is particularly important, as the brain is a critical organ with little adaptability. Brain growth mainly depends on neural stem cell (NSC) proliferation to generate differentiated neural cells, it is however unclear how organism developmental progression is coordinated with NSCs.

Asynchronous transcription and translation of neurotransmitter-related genes characterize the initial stages of neuronal maturation in Drosophila.

Neuron specification and maturation are essential for proper central nervous system development. However, the precise mechanisms that govern neuronal maturation, essential to shape and maintain neuronal circuitry, remain poorly understood. Here, we analyse early-born secondary neurons in the Drosophila larval brain, revealing that the early maturation of secondary neurons goes through 3 consecutive phases: (1) Immediately after birth, neurons express pan-neuronal markers but do not transcribe terminal differentiation genes; (2) Transcription of terminal differentiation genes, such as neurotransmitter-related genes VGlut, ChAT, or Gad1, starts shortly after neuron birth, but these transcripts are, however, not translated; (3) Translation of neurotransmitter-related genes only begins several hours later in mid-pupa stages in a coordinated manner with animal developmental stage, albeit in an ecdysone-independent manner.

Serine hydroxymethyl transferase is required for optic lobe neuroepithelia development in Drosophila.

Cell fate and growth require one-carbon units for the biosynthesis of nucleotides, methylation reactions and redox homeostasis, provided by one-carbon metabolism. Consistently, defects in one-carbon metabolism lead to severe developmental defects, such as neural tube defects. However, the role of this pathway during brain development and in neural stem cell regulation is poorly understood.

dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth.

Tumor cells have an increased demand for nutrients to sustain their growth, but how these increased metabolic needs are ensured or how this influences tumor formation and progression remains unclear. To unravel tumor metabolic dependencies, particularly from extracellular metabolites, we have analyzed the role of plasma membrane metabolic transporters in Drosophila brain tumors. Using a well-established neural stem cell-derived tumor model, caused by brat knockdown, we have found that 13 plasma membrane metabolic transporters, including amino acid, carbohydrate and monocarboxylate transporters, are upregulated in tumors and are required for tumor growth.

aPKC regulates apical constriction to prevent tissue rupture in the Drosophila follicular epithelium.

Apical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Dysregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncover how Drosophila aPKC maintains epithelial architecture by directly observing tissue disorganization after fast optogenetic inactivation in living adult flies and ovaries cultured ex vivo.

Function of Proneural Genes Ascl1 and Asense in Neurogenesis: How Similar Are They?

Proneural genes were initially identified in , where pioneer work on these important regulators of neural development was performed, and from which the term proneural function was coined. Subsequently, their counterparts in vertebrates were identified, and their function in neural development extensively characterized. The function of proneural transcription factors in flies and vertebrates is, however, very distinct.

Mitochondrial Dynamics in the Ovary Regulates Germ Stem Cell Number, Cell Fate, and Female Fertility.

The fate and proliferative capacity of stem cells have been shown to strongly depend on their metabolic state. Mitochondria are the powerhouses of the cell being responsible for energy production oxidative phosphorylation (OxPhos) as well as for several other metabolic pathways. Mitochondrial activity strongly depends on their structural organization, with their size and shape being regulated by mitochondrial fusion and fission, a process known as mitochondrial dynamics.

Integrating animal development: How hormones and metabolism regulate developmental transitions and brain formation.

Our current knowledge on how individual tissues or organs are formed during animal development is considerable. However, the development of each organ does not occur in isolation and thus their formation needs to be done in a coordinated manner. This coordination is regulated by hormones, systemic signals that instruct the simultaneous development of all organs and direct tissue specific developmental programs.

Proliferation control in neural stem and progenitor cells.

Neural circuit function can be drastically affected by variations in the number of cells that are produced during development or by a reduction in adult cell number owing to disease. For this reason, unique cell cycle and cell growth control mechanisms operate in the developing and adult brain. In Drosophila melanogaster and in mammalian neural stem and progenitor cells, these mechanisms are intricately coordinated with the developmental age and the nutritional, metabolic and hormonal state of the animal.

Ecdysone and mediator change energy metabolism to terminate proliferation in Drosophila neural stem cells.

Stem cells are highly abundant during early development but become a rare population in most adult organs. The molecular mechanisms causing stem cells to exit proliferation at a specific time are not well understood. Here, we show that changes in energy metabolism induced by the steroid hormone ecdysone and the Mediator initiate an irreversible cascade of events leading to cell-cycle exit in Drosophila neural stem cells.

SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells.

Members of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in human cancer, but how they suppress tumorigenesis is currently unclear. Here, we use Drosophila neuroblasts to demonstrate that the SWI/SNF component Osa (ARID1) prevents tumorigenesis by ensuring correct lineage progression in stem cell lineages. We show that Osa induces a transcriptional program in the transit-amplifying population that initiates temporal patterning, limits self-renewal, and prevents dedifferentiation.

Long-term live cell imaging and automated 4D analysis of drosophila neuroblast lineages.

The developing Drosophila brain is a well-studied model system for neurogenesis and stem cell biology. In the Drosophila central brain, around 200 neural stem cells called neuroblasts undergo repeated rounds of asymmetric cell division. These divisions typically generate a larger self-renewing neuroblast and a smaller ganglion mother cell that undergoes one terminal division to create two differentiating neurons.

Drosophila neuroblasts: a model for stem cell biology.

Drosophila neuroblasts, the stem cells of the developing fly brain, have emerged as a key model system for neural stem cell biology and have provided key insights into the mechanisms underlying asymmetric cell division and tumor formation. More recently, they have also been used to understand how neural progenitors can generate different neuronal subtypes over time, how their cell cycle entry and exit are coordinated with development, and how proliferation in the brain is spared from the growth restrictions that occur in other organs upon starvation. In this Primer, we describe the biology of Drosophila neuroblasts and highlight the most recent advances made using neuroblasts as a model system.

Exploring the roles of diaphanous and enabled activity in shaping the balance between filopodia and lamellipodia.

During migration cell protrusions power cell extension and sample the environment. Different cells produce different protrusions, from keratocytes dominated by lamellipodia, to growth cones combining filopodia and lamellipodia, to dendritic spines. One key challenge is to determine how the toolkit of actin regulators are coordinated to generate these diverse protrusive arrays.

Enabled and Capping protein play important roles in shaping cell behavior during Drosophila oogenesis.

During development, cells craft an impressive array of actin-based structures, mediating events as diverse as cytokinesis, apical constriction, and cell migration. One challenge is to determine how cells regulate actin assembly and disassembly to carry out these cell behaviors. During Drosophila oogenesis diverse cell behaviors are seen in the soma and germline.

Diaphanous regulates myosin and adherens junctions to control cell contractility and protrusive behavior during morphogenesis.

Formins are key regulators of actin nucleation and elongation. Diaphanous-related formins, the best-known subclass, are activated by Rho and play essential roles in cytokinesis. In cultured cells, Diaphanous-related formins also regulate cell adhesion, polarity and microtubules, suggesting that they may be key regulators of cell shape change and migration during development.

Using Bcr-Abl to examine mechanisms by which abl kinase regulates morphogenesis in Drosophila.

Signaling by the nonreceptor tyrosine kinase Abelson (Abl) plays key roles in normal development, whereas its inappropriate activation helps trigger the development of several forms of leukemia. Abl is best known for its roles in axon guidance, but Abl and its relatives also help regulate embryonic morphogenesis in epithelial tissues. Here, we explore the role of regulation of Abl kinase activity during development.

Rho1 regulates Drosophila adherens junctions independently of p120ctn.

During animal development, adherens junctions (AJs) maintain epithelial cell adhesion and coordinate changes in cell shape by linking the actin cytoskeletons of adjacent cells. Identifying AJ regulators and their mechanisms of action are key to understanding the cellular basis of morphogenesis. Previous studies linked both p120catenin and the small GTPase Rho to AJ regulation and revealed that p120 may negatively regulate Rho.