Biology subjects

Doe, C. Q.

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

At least 19 recordsLinked to original sources

bioRxiv2025

The Fd4 transcription factor translates transient spatial cues in progenitors into long-term lineage identity

Neural diversity is required for the brain to generate complex behaviors. During development, neural progenitors are exposed to different combination of transient spatial cues for their identity specification. This identity is then interpreted by their progeny to activate terminal selector genes to become lineage-specific neurons. After spatial cues fade, it remains unclear how progenitors maintain their unique identity so that their progeny express the accurate, lineage-specific terminal selector genes. Using single cell RNA sequencing in Drosophila, we identified a Forkhead domain transcription factor, Fd4, that is exclusively expressed in a single neural progenitor (neuroblast) and its new-born progeny. This neuroblast (NB), named NB7-1, forms at the intersection of the transient spatial cues Vnd (columnar expression) and En (row expression). We show that Fd4 expression overlaps spatial factor expression and terminal selector gene expression, thereby making Fd4 an excellent candidate for bridging transient spatial factors to lineage-specific terminal selector genes. We show that Fd4 is required for expression of terminal selector genes that maintain neuronal identity. Conversely, Fd4 misexpression generates ectopic NB7-1 progeny at the expense of Fd4-negative progenitor lineages. We conclude that Fd4 is continuously expressed in the NB7-1 and its new-born neuronal progeny where it activates terminal selector genes to produce lineage-specific neurons. We propose that Fd4 is a pioneering member of a class of "lineage identity genes" that translate transient spatial cues into a long-term lineage identity.

developmental biology↗

bioRxiv2025

Vnd and En are expressed in orthogonal stripes and act in a brief competence window to combinatorially specify NB7-1 and its early lineage

Understanding how neuronal diversity is generated is a major goal of neuroscience. Here we characterize the first step in generating neuronal diversity in the Drosophila embryo: spatial transcription factors (STFs) expressed in orthogonal rows and columns of neural progenitors. These factors give spatial identity to neural progenitors (neuroblasts, NBs), and are highly conserved in mammals. Here we investigate the roles of Engrailed (En+; posterior row) and Vnd+ (medial column) in specifying the well-characterized progenitor: neuroblast 7-1 (NB7-1). We show that NB7-1 is located at the intersection of Vnd and En, and we identify NB7-1 using a newly characterized gene, fd4, that we show is specifically expressed in NB7-1 and its progeny, giving us a specific assay for NB7-1 identity. We show that En and Vnd are both required for Fd4 expression, and that Vnd and En co-expression is sufficient to induce ectopic Fd4 expression in other NBs and their lineages. Finally, we show that NBs gradually lose competence to respond to En or Vnd. We conclude that En and Vnd are STFs that act combinatorially to specify the identity of an individual progenitor, NB7-1.

developmental biology↗

bioRxiv2025

Hunchback functions in the post-mitotic larval MDN to restrict axon outgrowth, synapse formation, and backward locomotion

During neurodevelopment, a single progenitor cell can generate many different neuron types. As these neurons mature, they form unique morphologies, integrate into neural circuits, and contribute to behavior. However, the integration of these developmental events is understudied. Here, we show that the same transcription factor is important for both the generation of neuronal diversity and maintaining mature neuronal identity, providing novel insights on how the generation of neuronal identity and morphology are coordinated. We utilized a previously characterized larval locomotor circuit in Drosophila, where activation of the Moonwalker Descending Neuron (MDN) triggers backward locomotion via its presynaptic connection with the premotor neuron A18b. MDN expresses the temporal transcription factor Hunchback (Hb), which has a well-characterized role in neural progenitors. Loss of Hb in the post-mitotic MDN increases axon/dendrite branching, leading to additional functional synapses on A18b and increasing backward locomotion. We conclude that the endogenous function of Hb is to restrain axon/dendrite outgrowth, including limiting MDN-A18b synapses, thereby dampening backward locomotion. Our work provides insights on how a transcription factor can have different functions throughout life - i.e. Hb generates neuronal diversity in the progenitor and regulates neuronal connectivity in the mature neuron to generate an appropriately tuned behavior.

neuroscience↗

bioRxiv2024

The Hunchback temporal transcription factor determines interneuron molecular identity, morphology, and presynapse targeting in the Drosophila NB5-2 lineage

Interneuron diversity within the central nervous system (CNS) is essential for proper circuit assembly. Functional interneurons must integrate multiple features, including combinatorial transcription factor (TF) expression, axon/dendrite morphology, and connectivity to properly specify interneuronal identity. Yet, how these different interneuron properties are coordinately regulated remains unclear. Here we used the Drosophila neural progenitor, NB5-2, known to generate late-born interneurons in a proprioceptive circuit, to determine if the early-born temporal transcription factor (TTF), Hunchback (Hb), specifies early-born interneuron identity, including molecular profile, axon/dendrite morphology, and presynapse targeting. We found that prolonged Hb expression in NB5-2 increases the number of neurons expressing early-born TFs (Nervy, Nkx6, and Dbx) at the expense of late-born TFs (Runt and Zfh2); thus, Hb is sufficient to promote interneuron molecular identity. Hb is also sufficient to transform late-born neuronal morphology to early-born neuronal morphology. Furthermore, prolonged Hb promotes the relocation of late-born neuronal presynapses to early-born neuronal presynapse neuropil locations, consistent with a change in interneuron connectivity. Finally, we found that prolonged Hb expression led to defects in proprioceptive behavior, consistent with a failure to properly specify late-born interneurons in the proprioceptive circuit. We conclude that the Hb TTF is sufficient to specify multiple aspects of early-born interneuron identity, as well as disrupt late-born proprioceptive neuron function.

developmental biology↗

bioRxiv2024

Castor is a temporal transcription factor that specifies early born central complex neuron identity

The generation of neuronal diversity is important for brain function, but how diversity is generated is incompletely understood. We used the development of the Drosophila central complex (CX) to address this question. The CX develops from eight bilateral Type 2 neuroblasts (T2NBs), which generate hundreds of different neuronal types. T2NBs express broad opposing temporal gradients of RNA-binding proteins. It remains unknown whether these protein gradients are sufficient to directly generate all known neuronal diversity, or whether there are temporal transcription factors (TTFs) with narrow expression windows that each specify a small subset of CX neuron identities. Multiple candidate TTFs have been identified, but their function remains uncharacterized. Here, we show that: (i) the adult E-PG neurons are born from early larval T2NBs; (ii) the candidate TTF Castor is expressed transiently in early larval T2NBs when E-PG and P-EN neurons are born; and (iii) that Castor is required to specify early born E-PG and P-EN neuron identities. We conclude that Castor is a TTF in larval T2NB lineages that specifies multiple, early born CX neuron identities. SummaryCastor acts in Type 2 neuroblast lineages as a temporal transcription factor to specify adult central complex columnar neuron identity.

developmental biology↗

bioRxiv2023

Seven-up acts in neuroblasts to specify adult central complex neuron identity and initiate neuroblast decommissioning

An open question in neurobiology is how diverse neuron cell types are generated from a small number of neural stem cells. In the Drosophila larval central brain, there are eight bilateral Type 2 neuroblast (T2NB) lineages that express a suite of early temporal factors followed by a different set of late temporal factors and generate the majority of the central complex (CX) neurons. The early-to-late switch is triggered by the orphan nuclear hormone receptor Seven-up (Svp), yet little is known about this Svp-dependent switch in specifying CX neuron identities. Here, we (i) birthdate the CX neurons P-EN and P-FN (early and late, respectively); (ii) show that Svp is transiently expressed in all early T2NBs; and (iii) show that loss of Svp expands the population of early born P-EN neurons at the expense of late born P-FN neurons. Furthermore, in the absence of Svp, T2NBs fail decommissioning and abnormally extend their lineage into week-old adults. We conclude that Svp is required to specify CX neuron identity, as well as to initiate T2NB decommissioning. SummarySeven-up acts in Type 2 neuroblasts to specify adult central complex columnar neuron identity and to initiate neuroblast decommissioning.

developmental biology↗

bioRxiv2023

Notch signaling and Bsh homeodomain activity are integrated to diversify Drosophila lamina neuron types

Notch signaling is an evolutionarily conserved pathway for specifying binary neuronal fates, yet how it specifies different fates in different contexts remains elusive. In our accompanying paper, using the Drosophila lamina neuron types (L1-L5) as a model, we show that the primary homeodomain transcription factor (HDTF) Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates. Here we test the hypothesis that Notch signaling enables Bsh to differentially specify L4 and L5 fates. We show asymmetric Notch signaling between newborn L4 and L5 neurons, but they are not siblings; rather, Notch signaling in L4 is due to Delta expression in adjacent L1 neurons. While Notch signaling and Bsh expression are mutually independent, Notch is necessary and sufficient for Bsh to specify L4 fate over L5. The NotchON L4, compared to NotchOFF L5, has a distinct open chromatin landscape which allows Bsh to bind distinct genomic loci, leading to L4-specific identity gene transcription. We propose a novel model in which Notch signaling is integrated with the primary HDTF activity to diversify neuron types by directly or indirectly generating a distinct open chromatin landscape that constrains the pool of genes that a primary HDTF can activate.

developmental biology↗

bioRxiv2022

Presynaptic contact and activity opposingly regulate postsynaptic dendrite outgrowth

The organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously we developed a model system in the Drosophila ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly and robustly respond to developmental variability in presynaptic location and input strength.

neuroscience↗

bioRxiv2022

Imp is required for timely exit from quiescence in Drosophila type II neuroblasts

Stem cells must balance proliferation and quiescence, with excess proliferation favoring tumor formation, and premature quiescence preventing proper organogenesis. Drosophila brain neuroblasts are a model for investigating neural stem cell entry and exit from quiescence. Neuroblasts begin proliferating during embryogenesis, enter quiescence prior to larval hatching, and resume proliferation 12-30h after larval hatching. Here we focus on the mechanism used to exit quiescence, focusing on the "type II" neuroblasts. There are 16 type II neuroblasts in the brain, and they undergo the same cycle of embryonic proliferation, quiescence, and proliferation as do most other brain neuroblasts. We focus on type II neuroblasts due to their similar lineage as outer radial glia in primates (both have extended lineages with intermediate neural progenitors) and because of the availability of specific markers for type II neuroblasts and their progeny. Here we characterize the role of Insulin-like growth factor II mRNA-binding protein (Imp) in type II neuroblast proliferation and quiescence. Imp has previously been shown to promote proliferation in type II neuroblasts, in part by acting antagonistically to another RNA-binding protein called Syncrip (Syp). Here we show that reducing Imp levels delays neuroblast exit from quiescence in type II neuroblasts, acting independently of Syp, with Syp levels remaining low in both quiescent and newly proliferating type II neuroblasts. We conclude that Imp promotes exit from quiescence, a function closely related to its known role in promoting neuroblast proliferation.

developmental biology↗

bioRxiv2021

Hunchback activates Bicoid in post-mitotic Pair1 neurons to regulate synapse number

The proper formation and function of neural circuits is crucial for cognition, sensation, and behavior. Neural circuits are highly-specific, and this specificity is dependent on neurons developing key features of their individual identities: morphology, anatomical location, molecular expression and biophysiological properties. Previous research has demonstrated that a neurons identity is, in part, generated by the temporal transcription window the neuron is born in, and the homeodomain transcription factors expressed in the mature neuron. However, whether temporal transcription factors and homeodomain transcription factors regulate neural circuit formation, maintenance and function remains unknown. Here, we utilize a well-characterized neural circuit in the Drosophila larvae, the Pair1 neuron. We determined that in the Pair1 neuron, the temporal transcription factor Hunchback activates the homeodomain transcription factor Bicoid (Bcd). Both Hunchback and Bcd are expressed in Pair1 throughout larval development. Interestingly, Hunchback and Bcd were not required in Pair1 for neurotransmitter identity or axonal morphology, but were required for synapse density. We found that these transcription factors were functioning post-mitotically in Pair1 to regulate synapse density. Additionally, knocking down Hunchback and Bcd in Pair1 neurons disrupted the behavioral output of the circuit. We utilized the genetic tool TransTango to determine that Hunchback function in Pair1 is to repress forming synapses with erroneous neurons. To our knowledge, these data are the first to show Hunchback activating Bcd expression, as well as the first to demonstrate a role for Hunchback and Bcd post-mitotically.

neuroscience↗

bioRxiv2021

Synapse-associated astrocyte mitochondria stabilize motor circuits to prevent excitotoxicity

Neurons have an outsized metabolic demand, requiring continuous metabolic support from non-neuronal cells called glia. When this support fails, toxic metabolic byproducts accumulate, ultimately leading to excitotoxicity and neurodegeneration. Astrocytes, the primary synapse-associated glial cell type, are known to provide essential metabolites (e.g. lactate) to sustain neuronal function. Here, we leverage the well-characterized Drosophila motor circuit to investigate another means of astrocyte-to-neuron metabolic support: activity-dependent trafficking of astrocyte mitochondria. Following optogenetic activation, motor neuron mitochondria migrate away from synapses. By contrast, astrocytic mitochondria accumulated peri-synaptically, and at times, were transferred into neighboring neurons. A genetic screen identified the mitochondrial adaptor protein Milton as a key regulator of this process. Astrocyte-specific milton knockdown disrupted regular mitochondrial trafficking, resulting in locomotor deficits, dysfunctional motor activity, and altered synapse number at the neuromuscular junction. These findings suggest that astrocytes dynamically redistribute mitochondria to buffer metabolic demand at synapses, highlighting a potential mechanism by which glia protect neural circuits from metabolic failure and neurodegeneration.

neuroscience↗

bioRxiv2021

A locomotor neural circuit persists and functions similarly in larvae and adult Drosophila

Individual neurons can undergo drastic structural changes, known as neuronal remodeling or structural plasticity. One example of this is in response to hormones, such as during puberty in mammals or metamorphosis in insects. However, in each of these examples it remains unclear whether the remodeled neuron resumes prior patterns of connectivity, and if so, whether the persistent circuits drive similar behaviors. Here, we utilize a well-characterized neural circuit in the Drosophila larva: the Moonwalking Descending Neuron (MDN) circuit. We previously showed that larval MDN induces backward crawling, and synapses onto the Pair1 interneuron to inhibit forward crawling (Carreira-Rosario et al., 2018). MDN is remodeled during metamorphosis and regulates backward walking in the adult fly. We investigated whether Pair1 is remodeled during metamorphosis and functions within the MDN circuit during adulthood. We assayed morphology and molecular markers to demonstrate that Pair1 is remodeled during metamorphosis and persists in the adult fly. In the adult, optogenetic activation of Pair1 resulted in arrest of forward locomotion, similar to what is observed in larvae. MDN and Pair1 are also synaptic partners in the adult, showing that the MDN-Pair1 interneuron circuit is retained in the adult following hormone-driven pupal remodeling. Thus, the MDN-Pair1 neurons are an interneuronal circuit - i.e. a pair of synaptically connected interneurons - that persists through metamorphosis, taking on new input/output neurons, yet generating similar locomotor behavior at both stages.

neuroscience↗

bioRxiv2021

Mechanosensory input shapes Drosophila motor behavior through Patterned Spontaneous Network Activity

Neural activity sculpts circuit wiring in many animals. In vertebrates, patterned spontaneous network activity (PaSNA) generates sensory maps and establishes local circuits 1-3. However, it remains unclear how PaSNA might shape neuronal circuits and behavior in invertebrates. Previous work in the developing Drosophila embryo discovered spontaneous muscle activity that did not require synaptic transmission, and hence was myogenic, preceding PaSNA 4-6. These studies, however, monitored muscle movement, not neural activity, and were therefore unable to observe how myogenic activity might relate to subsequent neural network engagement. Here we use calcium imaging to directly record neural activity and characterize the emergence of PaSNA. We demonstrate that the spatiotemporal properties of PaSNA are highly stereotyped across embryos, arguing for genetic programming. Consistent with previous observations, we observe neural activity well before it becomes patterned, initially emerging during the myogenic stage. Remarkably, inhibition of mechanosensory input as well as inhibition of muscle contractions results in premature and excessive PaSNA, demonstrating that muscle movement serves as a brake on this process. Finally, using an optogenetic strategy to selectively disrupt mechanosensory inputs during PaSNA, followed by quantitative modeling of larval behavior, we demonstrate that mechanosensory modulation during development is required for proper larval foraging. This work thus provides a foundation for using the Drosophila embryo to study the role of PaSNA in circuit formation, provides mechanistic insight into how PaSNA is entrained by motor activity, and demonstrates that spontaneous network activity is essential for locomotor behavior. These studies argue that sensory feedback during the earliest stages of circuit formation can sculpt locomotor behaviors through innate motor learning. HighlightsO_LIPaSNA in the Drosophila embryonic CNS is spatiotemporally stereotyped C_LIO_LIMechanosensory neurons negatively modulate PaSNA C_LIO_LIEmbryonic PaSNA is required for larval locomotor behavior C_LI

neuroscience↗

bioRxiv2020

Astrocytes close a critical period of motor circuit plasticity

Critical periods - brief intervals where neural circuits can be modified by sensory input - are necessary for proper neural circuit assembly. Extended critical periods are associated with neurodevelopmental disorders, including schizophrenia and autism; however, the mechanisms that ensure timely critical period closure remain unknown. Here, we define the extent of a critical period in the developing Drosophila motor circuit, and identify astrocytes as essential for proper critical period termination. During the critical period, decreased activity produces larger motor dendrites with fewer inhibitory inputs; conversely, increased motor neuron activity produces smaller motor dendrites with fewer excitatory inputs. Importantly, activity has little effect on dendrite morphology after critical period closure. Astrocytes invade the neuropil just prior to critical period closure, and astrocyte ablation prolongs the critical period. Finally, we use a genetic screen to identify astrocyte-motor neuron signaling pathways that close the critical period, including Neuroligin-Neurexin signaling. Reduced signaling destabilizes dendritic microtubules, increases dendrite dynamicity, and impairs locomotor behavior, underscoring the importance of critical period closure. Previous work defines astroglia as regulators of plasticity at individual synapses; here, we show that astrocytes also regulate large-scale structural plasticity to motor dendrite, and thus, circuit architecture to ensure proper locomotor behavior.

neuroscience↗

bioRxiv2020

A novel temporal identity window generates alternating cardinal motor neuron subtypes in a single progenitor lineage

Spatial patterning specifies neural progenitor identity, with further diversity generated by temporal patterning within individual progenitor lineages. These mechanisms generate cardinal classes of motor neurons (sharing a transcription factor identity and common muscle group targets). In Drosophila, two cardinal classes are Even-skipped (Eve)+ motor neurons projecting to dorsal muscles and Nkx6+ motor neurons projecting to ventral muscles. The Drosophila neuroblast 7-1 (NB7-1) lineage generates distinct Eve+ motor neurons via the temporal transcription factor (TTF) cascade Hunchback (Hb)-Kruppel (Kr)-Pdm-Castor (Cas). Here we show that a newly discovered Kr/Pdm temporal identity window gives rise to an Nkx6+ Eve-motor neuron projecting to ventral oblique muscles, resulting in alternation of cardinal motor neuron subtypes from a single progenitor (Eve>Nkx6>Eve). We show that co-overexpression of Kr/Pdm generates ectopic VO motor neurons within the NB7-1 lineage and that Kr/Pdm act via Nkx6, which itself is necessary and sufficient for VO motor neuron identity. Lastly, Nkx6 is required for ventral oblique muscle targeting, thereby linking temporal patterning to motor neuron morphology and synaptic target selection. In conclusion, we show that one neuroblast lineage generates interleaved cardinal motor neurons fates; that the Kr/Pdm TTFs form a novel temporal identity window that promotes expression of Nkx6; and that the Kr/Pdm>Nkx6 pathway is necessary and sufficient to specify VO motor neuron identity and morphology.

developmental biology↗

bioRxiv2019

Effects of nectin-3 misexpression on dendritic spine density during the postnatal development of layer 2/3 cortical neurons

BackgroundDeveloping cortical neurons express a tightly choreographed sequence of cytoskeletal and transmembrane proteins to form and strengthen specific synaptic connections during circuit formation. Nectin-3 is a cell-adhesion molecule with previously described roles in synapse formation and maintenance. This protein and its binding partner, Nectin-1, are selectively expressed in upper-layer neurons of mouse visual cortex, but their role in the development of cortical circuits is unknown. MethodsHere we block Nectin-3 expression (via shRNA) or overexpress Nectin-3 in developing layer 2/3 visual cortical neurons using in utero electroporation. We then assay dendritic spine densities at three developmental time points: eye opening (postnatal day (P)14), one week following eye opening after a period of heightened synaptogenesis (P21), and at the close of the critical period for ocular dominance plasticity (P35). ResultsKnockdown of Nectin-3 beginning at E15.5 or [~]P19 increased dendritic spine densities at P21 or P35, respectively. Conversely, overexpressing full length Nectin-3 at E15.5 led to decreased dendritic spine densities when all ages were considered together. Interestingly, an even greater decrease in dendritic spine densities, particularly at P21, was observed when we overexpressed Nectin-3 lacking its Afadin binding domain, indicating Afadin may facilitate spine morphogenesis after eye opening. ConclusionThese data collectively suggest that the proper levels of Nectin-3, as well as the interaction of Nectin-3 with Afadin, facilitate normal synapse formation after eye opening in layer 2/3 visual cortical neurons.

neuroscience↗

bioRxiv2019

Synaptic specificity is collectively determined by partner identity, location and activity

Our nervous system is organized into circuits with specifically matched and tuned cell-to-cell connections that are essential for proper function. The mechanisms by which presynaptic axon terminals and postsynaptic dendrites recognize each other and establish the correct number of connections are still incompletely understood. Sperrys chemoaffinity hypothesis proposes that pre- and postsynaptic partners express specific combinations of molecules that enable them to recognize each other. Alternatively, Peters rule proposes that presynaptic axons and postsynaptic dendrites use non-partner-derived global positional cues to independently reach their target area, and once there they randomly connect with any available neuron. These connections can then be further refined by additional mechanisms based on synaptic activity. We used the tractable genetic model system, the Drosophila embryo and larva, to test these hypotheses and elucidate the roles of 1) global positional cues, 2) partner-derived cues and 3) synaptic activity in the establishment of selective connections in the developing nerve cord. We altered the position or activity of presynaptic partners and analyzed the effect of these manipulations on the number of synapses with specific postsynaptic partners, strength of functional connections, and behavior controlled by these neurons. For this purpose, we combined developmental live imaging, electron microscopy reconstruction of circuits, functional imaging of neuronal activity, and behavioral experiments in wildtype and experimental animals. We found that postsynaptic dendrites are able to find, recognize, and connect to their presynaptic partners even when these have been shifted to ectopic locations through the overexpression of receptors for midline guidance cues. This suggests that neurons use partner-derived cues that allow them to identify and connect to each other. However, while partner-derived cues are sufficient for recognition between specific partners and establishment of connections;; without orderly positioning of axon terminals by positional cues and without synaptic activity during embryonic development, the numbers of functional connections are altered with significant consequences for behavior. Thus, multiple mechanisms including global positional cues, partner-derived cues, and synaptic activity contribute to proper circuit assembly in the developing Drosophila nerve cord.

neuroscience↗

bioRxiv2019

The role of lineage, hemilineage and temporal identity in establishing neuronal targeting and connectivity in the Drosophila embryo

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 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 circuit formation and function, and that these principles are broadly applicable throughout the nervous system.

neuroscience↗