Biology subjects

Doe, C. Q.

Publications and source records attributed to Doe, C. Q..

27 records · Page 2Linked to original sources

bioRxiv2019

A Drosophila larval premotor/motor neuron connectome generating two behaviors via distinct spatio-temporal muscle activity

Animals generate diverse motor behaviors, yet how the same motor neurons generate distinct behaviors remains an open question. Drosophila larvae have multiple behaviors - e.g. forward crawling, backward crawling, self-righting and escape - and all of the body wall motor neurons (MNs) driving these behaviors have been identified. Despite impressive progress in mapping larval motor circuits, the role of most motor neurons in locomotion remains untested, the majority of premotor neurons (PMNs) remain to be identified, and a full understanding of proprioceptor-PMN-MN connectivity is missing. Here we report a comprehensive larval proprioceptor-PMN-MN connectome; describe individual muscle/MN phase activity during both forward and backward locomotor behaviors; identify PMN-MN connectivity motifs that could generate muscle activity phase relationships, plus selected experimental validation; identify proprioceptor-PMN connectivity that provides an anatomical explanation for the role of proprioception in promoting locomotor velocity; and identify a new candidate escape motor circuit. Finally, we generate a recurrent network model that produces the observed sequence of motor activity, showing that the identified pool of premotor neurons is sufficient to generate two distinct larval behaviors. We conclude that different locomotor behaviors can be generated by a specific group of premotor neurons generating behavior-specific motor rhythms.

neuroscience↗

bioRxiv2019

Regulation of subcellular dendritic synapse specificity by axon guidance cues

Neural circuit assembly occurs with subcellular precision, yet the mechanisms underlying this precision remain largely unknown. Subcellular synaptic specificity could be achieved by molecularly distinct subcellular domains that locally regulate synapse formation, or by axon guidance cues restricting access to one of several acceptable targets. We address these models using two Drosophila neurons: the dbd sensory neuron and the A08a interneuron. In wild-type larvae, dbd synapses with the A08a medial dendrite but not the A08a lateral dendrite. dbd-specific overexpression of the guidance receptors Unc-5 or Robo-2 results in lateralization of the dbd axon, which forms anatomical and functional monosynaptic connections with the A08a lateral dendrite. We conclude that axon guidance cues, not molecularly distinct dendritic arbors, are a major determinant of dbd-A08a subcellular synapse specificity.

neuroscience↗

bioRxiv2019

The Hunchback temporal transcription factor determines motor neuron axon and dendrite targeting in Drosophila

The generation of neuronal diversity is essential for circuit formation and behavior. Morphological differences in sequentially born neurons could be due to intrinsic molecular identity specified by temporal transcription factors (henceforth called intrinsic temporal identity) or due to changing extrinsic cues. Here we use the Drosophila NB7-1 lineage to address this question. NB7-1 sequentially generates the U1-U5 motor neurons; each has a distinct intrinsic temporal identity due to inheritance of a different temporal transcription factor at time of birth. Here we show that the U1-U5 neurons project axons sequentially, followed by sequential dendrite extension. We misexpress the earliest temporal transcription factor, Hunchback, to create "ectopic" U1 neurons with an early intrinsic temporal identity but later birth-order. These ectopic U1 neurons have axon muscle targeting and dendrite neuropil targeting consistent with U1 intrinsic temporal identity, rather than their time of birth or differentiation. We conclude that intrinsic temporal identity plays a major role in establishing both motor axon muscle targeting and dendritic arbor targeting, which are required for proper motor circuit development.

neuroscience↗

bioRxiv2018

Temporal identity establishes columnar neuron morphology, connectivity, and function in a Drosophila navigation circuit

The insect central complex (CX) is a conserved brain region containing 60+ neuronal subtypes, several of which contribute to navigation. It is not known how CX neuronal diversity is generated or how developmental origin of subtypes relates to function. We mapped the developmental origin of four key CX subtypes and found that neurons with similar origin have matching axon/dendrite targeting. Moreover, we found that the temporal transcription factor (TTF) Eyeless/Pax6 regulates the development of two recurrently-connected CX subtypes: Eyeless loss simultaneously produces ectopic P-EN neurons with normal axon/dendrite projections, and reduces the number of E-PG neurons. Furthermore, the transient loss of Eyeless during development impairs adult flies capacity to perform celestial navigation. We conclude that neurons with similar developmental origin have similar connectivity, that Eyeless maintains equal E-PG and P-EN neuron number, and that Eyeless is required for the development of circuits that control adult navigation.

developmental biology↗

bioRxiv2018

Neuroblast-specific chromatin landscapes allow integration of spatial and temporal cues to generate neuronal diversity in Drosophila

During early neurogenesis in flies and mice, spatial and temporal cues interact to specify neuronal diversity, yet in no organism is it known how spatial and temporal cues are integrated. We used Targeted DamID (TaDa) to identify the genomic binding sites of the temporal transcription factor Hunchback in two adjacent Drosophila neuroblasts (NB5-6 and NB7-4). Hunchback targets were different in each neuroblast. Profiling chromatin accessibility showed that each neuroblast had a distinct chromatin landscape: Hunchback-bound loci in NB5-6 were in open chromatin, but the same loci in NB7-4 were in closed chromatin. Moreover, binding of the spatial factor Gsb/Pax3, essential for NB5-6 specification, was correlated with open chromatin and Hunchback-enriched loci in NB5-6, but not NB7-4. We propose early-acting spatial factors establish a unique chromatin landscape in each neuroblast, thereby restricting temporal factor binding to different loci in each neuroblast, resulting in different neurons in each neuroblast lineage.\n\nImpact statementIntegration of spatial and temporal identity during Drosophila neurogenesis is due to spatial factors generating neuroblast-specific chromatin thereby biasing subsequent temporal transcription factor binding and producing neuroblast-specific neurons.

developmental biology↗

bioRxiv2018

A repressor-decay timer for robust temporal patterning in embryonic Drosophila neuroblast lineages

Biological timers synchronize patterning processes during embryonic development. In the Drosophila embryo, neural progenitors (neuroblasts; NBs) produce a sequence of unique neurons whose identities depend on the sequential expression of temporal transcription factors (TTFs). The stereotypy and precision of the NB lineages indicate reproducible temporal progression of the TTF timer. To examine the basis of this robustness, we combine theory and experiments. The TTF timer is commonly described as a relay of activators, but its regulatory circuit is also consistent with a repressor-decay timer, in which expression of each TTF begins once its repressor is sufficiently reduced. We find that repressor-decay timers are more robust to parameter variations compared to activator-relay timers. This suggests that the in-vivo TTF sequence progresses primarily by repressor-decay, a prediction that we support experimentally. Our results emphasize the role of robustness in the evolutionary design of patterning circuits.

bioinformatics↗

bioRxiv2018

A command-like descending neuron that coordinately activates backward and inhibits forward locomotion

Command-like descending neurons can induce many behaviors, such as backward locomotion, escape, feeding, courtship, egg-laying, or grooming. In most animals it remains unknown how neural circuits switch between these antagonistic behaviors: via top-down activation/inhibition of antagonistic circuits or via reciprocal inhibition between antagonistic circuits. Here we use genetic screens, intersectional genetics, circuit reconstruction by electron microscopy, and functional optogenetics to identify a bilateral pair of larval \"mooncrawler descending neurons\" (MDNs) with command-like ability to coordinately induce backward locomotion and block forward locomotion; the former by activating a backward-specific premotor neuron, and the latter by disynaptic inhibition of a forward-specific premotor neuron. In contrast, direct reciprocal inhibition between forward and backward circuits was not observed. Thus, MDNs coordinate a transition between antagonistic larval locomotor behaviors. Interestingly, larval MDNs persist into adulthood, where they can trigger backward walking. Thus, MDNs induce backward locomotion in both limbless and limbed animals.\n\nHighlightsO_LIMDN command-like descending neuron induces backward larval locomotion\nC_LIO_LIMDN neurons coordinately regulate antagonistic behaviors (forward/backward locomotion)\nC_LIO_LIMDN-motor circuit validated at structural (TEM) and functional (optogenetic) levels\nC_LIO_LIMDN neurons induce backward locomotion in both limbless larva and limbed adult\nC_LI

neuroscience↗

bioRxiv2017

Drosophila embryonic type II neuroblasts: origin, temporal patterning, and contribution to the adult central complex

Drosophila neuroblasts are an excellent model for investigating how neuronal diversity is generated. Most brain neuroblasts generate a series of ganglion mother cells (GMCs) that each make two neurons (type I lineage), but sixteen brain neuroblasts generate a series of intermediate neural progenitors (INPs) that each produce 4-6 GMCs and 8-12 neurons (type II lineage). Thus, type II lineages are similar to primate cortical lineages, and may serve as models for understanding cortical expansion. Yet the origin of type II neuroblasts remains mysterious: do they form in the embryo or larva? If they form in the embryo, do their progeny populate the adult central complex, as do the larval type II neuroblast progeny? Here we present molecular and clonal data showing that all type II neuroblasts form in the embryo, produce INPs, and express known temporal transcription factors. Embryonic type II neuroblasts and INPs undergo quiescence, and produce embryonic-born progeny that contribute to the adult central complex. Our results provide a foundation for investigating the development of the central complex, and tools for characterizing early-born neurons in central complex function.

developmental biology↗

bioRxiv2017

Steroid Hormone Induction Of Temporal Gene Expression In Drosophila Brain Neuroblasts Generates Neuronal And Glial Diversity

An important question in neuroscience is how stem cells generate neuronal diversity. During Drosophila embryonic development, neural stem cells (neuroblasts) sequentially express transcription factors that generate neuronal diversity; regulation of the embryonic temporal transcription factor cascade is lineage-intrinsic. In contrast, larval neuroblasts generate longer {small tilde}50 division lineages, and currently only one mid-larval molecular transition is known: Chinmo/Imp/Lin-28+ neuroblasts transition to Syncrip+ neuroblasts. Here we show that the hormone ecdysone is required to down-regulate Chinmo/Imp and activate Syncrip, plus two late neuroblast factors, Broad and E93. We show that Seven-up triggers Chinmo/Imp to Syncrip/Broad/E93 transition by inducing expression of the Ecdysone receptor in mid-larval neuroblasts, rendering them competent to respond to the systemic hormone ecdysone. Importantly, late temporal gene expression is essential for proper neuronal and glial cell type specification. This is the first example of hormonal regulation of temporal factor expression in Drosophila embryonic or larval neural progenitors.\n\nSummaryHormone induction of temporal gene expression in neural progenitors

developmental biology↗