Determinants of motor neuron functional subtypes important for locomotor speed

Cell Reports, Год журнала: 2023, Номер 42(9), С. 113049 - 113049

Опубликована: Сен. 1, 2023

Locomotion requires precise control of the strength and speed muscle contraction is achieved by recruiting functionally distinct subtypes motor neurons (MNs). MNs are essential to movement differentially susceptible in disease, but little known about how acquire functional subtype-specific features during development. Using single-cell RNA profiling embryonic larval zebrafish, we identify novel conserved molecular signatures for MN genes expressed both early post-mitotic mature MNs. Assessing development genetic mutants, define a program subtype specification. Two evolutionarily transcription factors, Prdm16 Mecom, determinants integral fast Loss prdm16 or mecom causes develop transcriptional profiles innervation similar slow These results reveal diversity vertebrate axial demonstrate that specified through intrinsic codes.

Язык: Английский

---

The conserved RNA-binding protein Imp is required for the specification and function of olfactory navigation circuitry in Drosophila

Current Biology, Год журнала: 2024, Номер 34(3), С. 473 - 488.e6

Опубликована: Янв. 4, 2024

Complex behaviors depend on the precise developmental specification of neuronal circuits, but relationship between genetic programs for neural development, circuit structure, and behavioral output is often unclear. The central complex (CX) a conserved sensory-motor integration center in insects, which governs many higher-order largely derives from small number type II stem cells (NSCs). Here, we show that Imp, IGF-II mRNA-binding protein expressed NSCs, plays role specifying essential components CX olfactory navigation circuitry. We following: (1) multiple circuitry arise NSCs. (2) Manipulating Imp expression NSCs alters morphology these elements, with most potent effects neurons targeting ventral layers fan-shaped body (FB). (3) regulates Tachykinin-expressing FB input neurons. (4) required establishing proper neuropil structures. (5) Loss abolishes upwind orientation to attractive odor while leaving locomotion odor-evoked regulation movement intact. Taken together, our findings establish temporally gene can regulate behavior by developmentally regulating provides first step toward dissection its roles behavior.

Язык: Английский

---

Neuronal birthdate reveals topography in a vestibular brainstem circuit for gaze stabilization

Current Biology, Год журнала: 2023, Номер 33(7), С. 1265 - 1281.e7

Опубликована: Март 15, 2023

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within central projection nucleus that stabilizes gaze larval zebrafish. We first discovered both somatic position and stimulus selectivity follow neuron birthdate. Next, electron microscopy loss-of-function assays, found patterns of peripheral innervation were similarly organized by Finally, birthdate spatial axonal arborization synapse formation outputs. Collectively, find development reveals previously hidden organization input, processing, output layers highly conserved vertebrate sensorimotor circuit. The temporal uncover constrain mechanisms may specify fate, function, vestibulo-ocular reflex neurons. More broadly, our data suggest that, like invertebrates, assemble architecture.

Язык: Английский

---

Deep scRNA sequencing reveals a broadly applicable Regeneration Classifier and implicates antioxidant response in corticospinal axon regeneration

Neuron, Год журнала: 2023, Номер 111(24), С. 3953 - 3969.e5

Опубликована: Окт. 16, 2023

Despite substantial progress in understanding the biology of axon regeneration CNS, our ability to promote clinically important corticospinal tract (CST) after spinal cord injury remains limited. To understand regenerative heterogeneity, we conducted patch-based single-cell RNA sequencing on rare regenerating CST neurons at high depth following PTEN and SOCS3 deletion. Supervised classification with Garnett gave rise a Regeneration Classifier, which can be broadly applied predict potential diverse neuronal types across developmental stages or injury. Network analyses highlighted importance antioxidant response mitochondrial biogenesis. Conditional gene deletion validated role for NFE2L2 (or NRF2), master regulator response, regeneration. Our data demonstrate universal transcriptomic signature underlying vastly different populations illustrate that deep only hundreds phenotypically identified has power advance biology.

Язык: Английский

---

Context-dependent T-BOX transcription factor family: from biology to targeted therapy

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 4, 2024

Abstract T-BOX factors belong to an evolutionarily conserved family of transcription factors. not only play key roles in growth and development but are also involved immunity, cancer initiation, progression. Moreover, the same molecule exhibits different or even opposite effects various developmental processes tumor microenvironments. Understanding multiple context-dependent malignancies is vital for uncovering potential T-BOX-targeted therapy. We summarize physiological their pathological observed when expression dysregulated. discuss regulatory immune microenvironment (TIME) newly arising questions that remain unresolved. This review will help systematically comprehensively understanding role factor physiology, pathology, immunity. The intention provide valuable information support

Язык: Английский

---

Asymmetric retinal direction tuning predicts optokinetic eye movements across stimulus conditions

eLife, Год журнала: 2023, Номер 12

Опубликована: Март 17, 2023

Across species, the optokinetic reflex (OKR) stabilizes vision during self-motion. OKR occurs when ON direction-selective retinal ganglion cells (oDSGCs) detect slow, global image motion on retina. How oDSGC activity is integrated centrally to generate behavior remains unknown. Here, we discover mechanisms that contribute encoding in vertically tuned oDSGCs and leverage these findings empirically define signal transformation between output vertical behavior. We demonstrate contrast-sensitive asymmetric for types prefer opposite directions. These phenomena arise from interplay spike threshold nonlinearities differences synaptic input weights, including shifts balance of excitation inhibition. In behaving mice, neurophysiological observations, along with a central subtraction outputs, accurately predict trajectories across stimulus conditions. Thus, tuning competing sensory channels can critically shape

Язык: Английский

---

Cell-type specification in the retina: Recent discoveries from transcriptomic approaches

Current Opinion in Neurobiology, Год журнала: 2023, Номер 81, С. 102752 - 102752

Опубликована: Июль 25, 2023

Understanding the formation of complex nervous system hinges on decoding mechanism that specifies a vast array neuronal types, each endowed with unique morphology, physiology, and connectivity. As pivotal step towards addressing this problem, seminal work has been devoted to characterizing distinct types. In recent years, high-throughput, single-cell transcriptomic methods have enabled rapid inventory cell types in various regions system, retina exhibiting complete molecular characterization across many vertebrate species. This invaluable resource furnished fresh perspective for investigating principles cell-type specification, thereby advancing our understanding retinal development. Accordingly, review focuses most characterizations cells, particular focus amacrine cells ganglion cells. These investigations unearthed new insights into their specification.

Язык: Английский

---

Differential expression analysis identifies candidate synaptogenic molecules for wiring direction-selective circuits in the retina

Journal of Neuroscience, Год журнала: 2024, Номер unknown, С. e1461232024 - e1461232024

Опубликована: Март 21, 2024

An organizational feature of neural circuits is the specificity synaptic connections. A striking example direction-selective (DS) circuit retina. There are multiple subtypes DS retinal ganglion cells (DSGCs) that prefer motion along one four preferred directions. This computation mediated by selective wiring a single inhibitory interneuron, starburst amacrine cell (SAC), with each DSGC subtype preferentially receiving input from subset SAC processes. We hypothesize molecular basis this in part unique expression profiles subtypes. To test this, we first performed paired recordings isolated mouse retinas both sexes to determine postnatal day 10 (P10) represents age at which asymmetric synapses form. Second, RNA sequencing and differential analysis on P10 ON-OFF DSGCs tuned for either nasal or ventral identified candidates may promote direction-specific wiring. then used conditional knock-out strategy role candidate, secreted organizer cerebellin-4 (Cbln4), development tuning. Using two-photon calcium imaging, observed small deficit directional tuning among ventral-preferring lacking Cbln4, though whole-cell voltage-clamp did not identify significant change inputs. suggests Cbln4 does function primarily via cell-autonomous mechanism instruct circuits. Nevertheless, our transcriptomic candidate factors gaining insights into mechanisms circuit.

Язык: Английский

---

Motor neurons are dispensable for the assembly of a sensorimotor circuit for gaze stabilization

eLife, Год журнала: 2024, Номер 13

Опубликована: Апрель 22, 2024

Sensorimotor reflex circuits engage distinct neuronal subtypes, defined by precise connectivity, to transform sensation into compensatory behavior. Whether and how motor neuron populations specify the subtype fate and/or sensory connectivity of their pre-motor partners remains controversial. Here, we discovered that neurons are dispensable for proper in vestibular circuit stabilizes gaze. We first measured activity following projection after constitutive loss extraocular partners. observed normal responses topography indicative unchanged functional between neurons. Next, show remain anatomically molecularly poised connect appropriately with downstream Lastly, transcriptional signatures typify develop independently Our findings comprehensively overturn a long-standing model: gaze stabilization is retrogradely determined partner-derived signals. By defining contribution specification an archetypal sensorimotor circuit, our work speaks comparable processes spinal cord advances understanding principles neural development.

Язык: Английский

---

The RNA-binding protein, Imp specifies olfactory navigation circuitry and behavior inDrosophila

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 29, 2023

Abstract Complex behaviors depend on the precise developmental specification of neuronal circuits, but relationship between genetic programs for neural development, circuit structure, and behavioral output is often unclear. The central complex (CX) a conserved sensory-motor integration center in insects that governs many higher order largely derives from small number Type II stem cells. Here, we show Imp, IGF-II mRNA-binding protein expressed cells, specifies components CX olfactory navigation circuitry. We show: (1) multiple circuitry arise cells manipulating Imp expression alters morphology these elements, with most potent effects neurons targeting ventral layers fan-shaped body. (2) regulates Tachykinin expressing body input neurons. (3) neuropil structures. (4) Loss abolishes upwind orientation to attractive odor while leaving locomotion odor-evoked regulation movement intact. Taken together, our work establishes single temporally gene can regulate behavior through provides first step towards dissection its roles behavior.

Язык: Английский

---