Probing the dynamics of cell differentiation in a model of Drosophila neurogenesis (original) (raw)
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We have produced a model of genetic regulation to simulate how neuroblasts and sensory organ precursor (SOP) cells di erentiate from proneural clusters of equivalent cells. Parameters of the model (mainly gene interaction strengths) are optimized in order to t schematic patterns of expression, drawn from the literature, of genes that are involved in this process of cell fate speci cation.
A cellular automaton model for neurogenesis in Drosophila
Physica D: Nonlinear Phenomena, 1998
A cellular automaton (CA) is constructed for the formation of the central nervous system of the Drosophila embryo. This is an experimentally well-studied system in which complex interactions between neighbouring cells appear to drive their differentiation into different types. It appears that all the cells initially have the potential to become neuroblasts, and all strive to this end, but those which differentiate first block their as yet undifferentiated neighbours from doing so. The CA makes use of observational evidence for a lateral inhibition mechanism involving signalling products $ of the 'proneural' or neuralizing genes. The key concept of the model is that cells are continuously producing S, but the production rate is lowered by inhibitory signals received from neighbouring cells which have advanced further along the developmental pathway. Comparison with experimental data shows that it well accounts for the observed proportion of neuroectodermal cells delaminating as neuroblasts.
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The mechanisms specifying neuronal diversity are well characterized, yet it remains unclear how or if these mechanisms regulate neural circuit assembly. To address this, we mapped the developmental origin of 160 interneurons from seven bilateral neural progenitors (neuroblasts) and identify them in a synapse-scale TEM reconstruction of the Drosophila larval central nervous system. We find that lineages concurrently build the sensory and motor neuropils by generating sensory and motor hemilineages in a Notch-dependent manner. Neurons in a hemilineage share common synaptic targeting within the neuropil, which is further refined based on neuronal temporal identity. Connectome analysis shows that hemilineage-temporal cohorts share common connectivity. Finally, we show that proximity alone cannot explain the observed connectivity structure, suggesting hemilineage/temporal identity confers an added layer of specificity. Thus, we demonstrate that the mechanisms specifying neuronal diversity also govern circuit formation and function, and that these principles are broadly applicable throughout the nervous system.
A developmental framework linking neurogenesis and circuit formation in the Drosophila CNS
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The mechanisms specifying neuronal diversity are well-characterized, yet it remains unclear how or if these mechanisms regulate neural circuit assembly. To address this, we mapped the developmental origin of 160 interneurons from seven bilateral neural progenitors (neuroblasts), and identify them in a synapse-scale TEM reconstruction of theDrosophilalarval CNS. We find that lineages concurrently build the sensory and motor neuropils by generating sensory and motor hemilineages in a Notch-dependent manner. Neurons in a hemilineage share common synaptic targeting within the neuropil, which is further refined based on neuronal temporal identity. Connectome analysis shows that hemilineage-temporal cohorts share common connectivity. Finally, we show that proximity alone cannot explain the observed connectivity structure, suggesting hemilineage/temporal identity confers an added layer of specificity. Thus, we demonstrate that the mechanisms specifying neuronal diversity also govern circui...
Regulatory interactions during early neurogenesis in Drosophila
Developmental Genetics, 1996
During neurogenesis in Drosophila, ectodermal cells are endowed with the capacity to become neuronal precursors. Following their selection, these cells initiate neuronal lineage development and differentiation. The processes of neuronal precursor specification and neuronal lineage development require the activities of several groups of genes functioning in a complex, hierarchical regulatory network. Whereas the proneural genes promote neurogenic potential, neurogenic genes restrict the acquisition of this identity to a subset of ectodermal cells. Following their selection, these cells express the pan neural neuronal precursor genes and a set of neuronal lineage identity genes. While lineage identity genes allow the various lineages to acquire specific identities, neuronal precursor genes presumably regulate functional and developmental characteristics common to all neuronal precursor cells. 0 1996 Wiley-Liss, Inc.
Regulating neural proliferation in the Drosophila CNS
Current Opinion in Neurobiology, 2010
Neural stem and progenitor cells generate the central nervous system (CNS) in organisms as diverse as insects and mammals. In Drosophila, multipotent asymmetrically dividing progenitors called neuroblasts produce neurons and glia throughout the developing CNS. Nevertheless, the timewindows of mitotic activity, the division modes, the termination mechanisms and the lineage sizes of individual neuroblasts all vary considerably from region-to-region. Recent studies shed light on some of the mechanisms underlying this neuroblast diversity and, in particular, how proliferation is boosted in two brain regions. In the central brain, some specialised neuroblasts generate intermediate neural progenitors that can each divide multiple times, thus increasing overall lineage size. In the optic lobe, an alternative expansion strategy involves symmetrically dividing neuroepithelial cells generating large numbers of asymmetrically dividing neuroblasts. Evidence is also emerging for a cell-intrinsic timer that alters the properties of each neuroblast with increasing developmental age. The core mechanism corresponds to a series of transcription factors that coordinates temporal changes in neuronal/glial identity with transitions in neuroblast cell-cycle speed, entry into quiescence and, ultimately, with termination.
Temporal patterning of neural progenitors in Drosophila
Current topics in developmental biology, 2013
Drosophila has recently become a powerful model system to understand the mechanisms of temporal patterning of neural progenitors called neuroblasts (NBs). Two different temporal sequences of transcription factors (TFs) have been found to be sequentially expressed in NBs of two different systems: the Hunchback, Krüppel, Pdm1/Pdm2, Castor, and Grainyhead sequence in the Drosophila ventral nerve cord; and the Homothorax, Klumpfuss, Eyeless, Sloppy-paired, Dichaete, and Tailless sequence that patterns medulla NBs. In addition, the intermediate neural progenitors of type II NB lineages are patterned by a different sequence: Dichaete, Grainyhead, and Eyeless. These three examples suggest that temporal patterning of neural precursors by sequences of TFs is a common theme to generate neural diversity. Cross-regulations, including negative feedback regulation and positive feedforward regulation among the temporal factors, can facilitate the progression of the sequence. However, there are man...
The Drosophila neural lineages: a model system to study brain development and circuitry
Development Genes and Evolution, 2010
In Drosophila, neurons of the central nervous system are grouped into units called lineages. Each lineage contains cells derived from a single neuroblast. Due to its clonal nature, the Drosophila brain is a valuable model system to study neuron development and circuit formation. To better understand the mechanisms underlying brain development, genetic manipulation tools can be utilized within lineages to visualize, knock down, or over-express proteins. Here, we will introduce the formation and development of lineages, discuss how one can utilize this model system, offer a comprehensive list of known lineages and their respective markers, and then briefly review studies that have utilized Drosophila neural lineages with a look at how this model system can benefit future endeavors.
Developmental Biology, 2004
How is cell fate diversity reliably achieved during development? Insect sensory organs have been a favorable model system for investigating this question for over 100 years. They are constructed using defined cell lineages that generate a maximum of cell diversity with a minimum number of cell divisions, and display tremendous variety in their morphologies, constituent cell types, and functions. An unexpected realization of the past 5 years is that very diverse sensory organs in Drosophila are produced by astonishingly similar cell lineages, and that their diversity can be largely attributed to only a small repertoire of developmental processes. These include changes in terminal cell differentiation, cell death, cell proliferation, cell recruitment, cell -cell interactions, and asymmetric segregation of cell fate determinants during mitosis. We propose that most Drosophila sensory organs are built from an archetypal lineage, and we speculate about how this stereotyped pattern of cell divisions may have been built during evolution.