Different Subtypes Of Neurons Research Articles

Integration of spatially opposing cues by a single interneuron guides decision-making in C. elegans

The capacity of animals to respond to hazardous stimuli in their surroundings is crucial for their survival. In mammals, complex evaluations of the environment require large numbers and different subtypes of neurons. The nematode C.elegans avoids hazardous chemicals they encounter by reversing their direction of movement. How does the worms' compact nervous system process the spatial information and direct motion change? We show here that a single interneuron, AVA, receives glutamatergic excitatory and inhibitory signals from head and tail sensory neurons, respectively. AVA integrates the spatially distinct and opposing cues, whose output instructs the animal's behavioral decision. We further find that the differential activation of AVA stems from distinct localization of inhibitory and excitatory glutamate-gated receptors along AVA's process and from different threshold sensitivities of the sensory neurons. Our results thus uncover a cellular mechanism that mediates spatial computation of nociceptive cues for efficient decision-making in C.elegans.

New unexpected role for Wolfram Syndrome protein WFS1: a novel therapeutic target for Alzheimer's disease?

New unexpected role for Wolfram Syndrome protein WFS1: a novel therapeutic target for Alzheimer's disease?

Intracortical microstimulation pulse waveform and frequency recruits distinct spatiotemporal patterns of cortical neuron and neuropil activation

Objective. Neural prosthetics often use intracortical microstimulation (ICMS) for sensory restoration. To restore natural and functional feedback, we must first understand how stimulation parameters influence the recruitment of neural populations. ICMS waveform asymmetry modulates the spatial activation of neurons around an electrode at 10 Hz; however, it is unclear how asymmetry may differentially modulate population activity at frequencies typically employed in the clinic (e.g. 100 Hz). We hypothesized that stimulation waveform asymmetry would differentially modulate preferential activation of certain neural populations, and the differential population activity would be frequency-dependent. Approach. We quantified how asymmetric stimulation waveforms delivered at 10 or 100 Hz for 30 s modulated spatiotemporal activity of cortical layer II/III pyramidal neurons using in vivo two-photon and mesoscale calcium imaging in anesthetized mice. Asymmetry is defined in terms of the ratio of the duration of the leading phase to the duration of the return phase of charge-balanced cathodal- and anodal-first waveforms (i.e. longer leading phase relative to return has larger asymmetry). Main results. Neurons within 40–60 µm of the electrode display stable stimulation-induced activity indicative of direct activation, which was independent of waveform asymmetry. The stability of 72% of activated neurons and the preferential activation of 20%–90% of neurons depended on waveform asymmetry. Additionally, this asymmetry-dependent activation of different neural populations was associated with differential progression of population activity. Specifically, neural activity tended to increase over time during 10 Hz stimulation for some waveforms, whereas activity remained at the same level throughout stimulation for other waveforms. During 100 Hz stimulation, neural activity decreased over time for all waveforms, but decreased more for the waveforms that resulted in increasing neural activity during 10 Hz stimulation. Significance. These data demonstrate that at frequencies commonly used for sensory restoration, stimulation waveform alters the pattern of activation of different but overlapping populations of excitatory neurons. The impact of these waveform specific responses on the activation of different subtypes of neurons as well as sensory perception merits further investigation.

Downregulation of the schizophrenia risk-gene Dgcr2 alters early microcircuit development in the mouse medial prefrontal cortex.

Alterations in the generation, migration and integration of different subtypes of neurons in the medial prefrontal cortex (mPFC) microcircuit could play an important role in vulnerability to schizophrenia. Using in vivo cell‐type specific manipulation of pyramidal neurons (PNs) progenitors, we aim to investigate the role of the schizophrenia risk‐gene DiGeorge Critical Region 2 (Dgcr2) on cortical circuit formation in the mPFC of developing mice. This report describes how Dgcr2 knock down in upper‐layer PNs impacts the functional maturation of PNs and interneurons (INs) in the mPFC. First, we demonstrate that Dgcr2 knock‐down disrupts laminar positioning, dendritic morphology and excitatory activity of upper‐layer PNs. Interestingly, inhibitory activity is also modified in Dgcr2 knock‐down PNs, suggesting a broader microcircuit alteration involving interneurons. Further analyses show that the histological maturation of parvalbumin (PV) INs is not dramatically impaired, thus implying that other INs subtypes might be at play in the reported microcircuit alteration. Overall, this study unravels how local functional deficits of the early postnatal development of the mPFC can be induced by Dgcr2 knock‐down in PNs.

Transcription factor-based gene therapy to treat glioblastoma through direct neuronal conversion.

Objective:Glioblastoma (GBM) is the most prevalent and aggressive adult primary cancer in the central nervous system. Therapeutic approaches for GBM treatment are under intense investigation, including the use of emerging immunotherapies. Here, we propose an alternative approach to treat GBM through reprogramming proliferative GBM cells into non-proliferative neurons.Methods:Retroviruses were used to target highly proliferative human GBM cells through overexpression of neural transcription factors. Immunostaining, electrophysiological recording, and bulk RNA-seq were performed to investigate the mechanisms underlying the neuronal conversion of human GBM cells. An in vivo intracranial xenograft mouse model was used to examine the neuronal conversion of human GBM cells.Results:We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1 (NeuroD1), Neurogenin-2 (Neurog2), or Achaete-scute homolog 1 (Ascl1). Subtype characterization showed that the majority of Neurog2- and NeuroD1-converted neurons were glutamatergic, while Ascl1 favored GABAergic neuron generation. The GBM cell-converted neurons not only showed pan-neuronal markers but also exhibited neuron-specific electrophysiological activities. Transcriptome analyses revealed that neuronal genes were activated in glioma cells after overexpression of neural transcription factors, and different signaling pathways were activated by different neural transcription factors. Importantly, the neuronal conversion of GBM cells was accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models.Conclusions:These results suggest that GBM cells can be reprogrammed into different subtypes of neurons, leading to a potential alternative approach to treat brain tumors using in vivo cell conversion technology.

Classification of GABAergic neuron subtypes from the globus pallidus using wild-type and transgenic mice.

Classifying different subtypes of neurons in deep brain structures is a challenge and is crucial to better understand brain function. Understanding the diversity of neurons in the globus pallidus (GP), a brain region positioned to influence afferent and efferent information processing within basal ganglia, could help to explain a variety of brain functions. We present a classification of neurons from the GP using electrophysiological data from wild-type mice and confirmation using transgenic mice. This work will help researchers to identify specific neuronal subsets in the GP of wild-type mice when transgenic mice with labelled neurons are lacking. Classification of the extensive neuronal diversity in the brain is fundamental for neuroscience. The globus pallidus external segment (GPe), also referred to as the globus pallidus in rodents, is a large nucleus located in the core of the basal ganglia whose circuitry is implicated in action control, decision-making and reward. Although considerable progress has been made in characterizing different GPe neuronal subtypes, no work has directly attempted to characterize these neurons in non-transgenic mice. Here, we provide data showing the degree of overlap in expression of neuronal PAS domain protein (Npas1), LIM homeobox 6 (Lhx6), parvalbumin (PV) and transcription factor FoxP2 biomarkers in mouse GPe neurons. We used an unbiased statistical method to classify neurons based on electrophysiological properties from nearly 200 neurons from C57BL/6J mice. In addition, we examined the subregion distribution of the neuronal subtypes. Cluster analysis using firing rate and hyperpolarization-induced membrane potential sag variables revealed three distinct neuronal clusters: type 1, characterized by low firing rate and small sag potential; type 2, with low firing rate and larger sag potential; and type 3, with high firing rate and small sag potential. We used other electrophysiological variables and data from marker-expressing neurons to evaluate the clusters. We propose that the GPe GABAergic neurons should be classified into three subgroups: arkypallidal, low-firing prototypical and high-firing prototypical neurons. This work will help researchers identify GPe neuron subtypes when transgenic mice with labelled neurons cannot be used.

Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinson\u2019s disease

BackgroundParkinson’s disease (PD) is one of the most common neurodegenerative diseases, neuropathologically characterized by misfolded protein aggregation, called Lewy bodies and Lewy neurites. PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease.MethodsIn order to study PD pathology in the colon, we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein (α-syn) fused with the green fluorescent protein (GFP), under the endogenous mouse α-syn promoter.ResultsWe observed an age-dependent progressive expression and accumulation of α-syn-GFP in the enteric neurons of Meissner’s (submucosal) and Auerbach’s (myenteric) plexuses of the colon. Additionally, the phosphorylation of α-syn at serine 129 also increased with age and the aggregation of α-syn-GFP coincided with the appearance of motor deficits at 9 months of age. Furthermore, α-syn (-GFP) distinctly co-localized with different subtypes of neurons, as identified by immunohistochemical labeling of vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), and calretinin.ConclusionsOur results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model, which coincide with the appearance of motor deficits. Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction.

Identification of Ca2+ signaling components in neural stem/progenitor cells during differentiation into neurons and glia in intact and dissociated zebrafish neurospheres

The development of the CNS in vertebrate embryos involves the generation of different sub-types of neurons and glia in a complex but highly-ordered spatio-temporal manner. Zebrafish are commonly used for exploring the development, plasticity and regeneration of the CNS, and the recent development of reliable protocols for isolating and culturing neural stem/progenitor cells (NSCs/NPCs) from the brain of adult fish now enables the exploration of mechanisms underlying the induction/specification/differentiation of these cells. Here, we refined a protocol to generate proliferating and differentiating neurospheres from the entire brain of adult zebrafish. We demonstrated via RT-qPCR that some isoforms of ip3r, ryr and stim are upregulated/downregulated significantly in differentiating neurospheres, and via immunolabelling that 1,4,5-inositol trisphosphate receptor (IP3R) type-1 and ryanodine receptor (RyR) type-2 are differentially expressed in cells with neuron- or radial glial-like properties. Furthermore, ATP but not caffeine (IP3R and RyR agonists, respectively), induced the generation of Ca2+ transients in cells exhibiting neuron- or glial-like morphology. These results indicate the differential expression of components of the Ca2+-signaling toolkit in proliferating and differentiating cells. Thus, given the complexity of the intact vertebrate brain, neurospheres might be a useful system for exploring neurodegenerative disease diagnosis protocols and drug development using Ca2+ signaling as a read-out.

Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence.

During embryonic brain development, neural progenitor/stem cells (NPCs) sequentially give rise to different subtypes of neurons and glia via a highly orchestrated process. To accomplish the ordered generation of distinct progenies, NPCs go through multistep transitions of their developmental competence. The molecular mechanisms driving precise temporal coordination of these transitions remains enigmatic. Epigenetic regulation, including changes in chromatin structures, DNA methylation, and histone modifications, has been extensively investigated in the context of cortical neurogenesis. Recent studies of chemical modifications on RNA, termed epitranscriptomics, have also revealed their critical roles in neural development. In this review, we discuss advances in understanding molecular regulation of the sequential lineage specification of NPCs in the embryonic mammalian brain with a focus on epigenetic and epitranscriptomic mechanisms. In particular, the discovery of lineage-specific gene transcripts undergoing rapid turnover in NPCs suggests that NPC developmental fate competence is determined much earlier, before the final cell division, and is more tightly controlled than previously appreciated. We discuss how multiple regulatory systems work in harmony to coordinate NPC behavior and summarize recent findings in the context of a model of epigenetic and transcriptional prepatterning to explain NPC developmental competence.

Transcription and Signaling Regulators in Developing Neuronal Subtypes of Mouse and Human Enteric Nervous System

Background & AimsThe enteric nervous system (ENS) regulates gastrointestinal function via different subtypes of neurons, organized into fine-tuned neural circuits. It is not clear how cell diversity is created within the embryonic ENS; information required for development of cell-based therapies and models of enteric neuropathies. We aimed to identify proteins that regulate ENS differentiation and network formation.MethodsWe generated and compared RNA expression profiles of the entire ENS, ENS progenitor cells, and non-ENS gut cells of mice, collected at embryonic days 11.5 and 15.5, when different subtypes of neurons are formed. Gastrointestinal tissues from R26ReYFP reporter mice crossed to Sox10-CreERT2 or Wnt1-Cre mice were dissected and the 6 populations of cells were isolated by flow cytometry. We used histochemistry to map differentially expressed proteins in mouse and human gut tissues at different stages of development, in different regions. We examined enteric neuronal diversity and gastric function in Wnt1-Cre x Sox6fl/fl mice, which do not express the Sox6 gene in the ENS.ResultsWe identified 147 transcription and signaling factors that varied in spatial and temporal expression during development of the mouse ENS. Of the factors also analyzed in human ENS, most were conserved. We uncovered 16 signaling pathways (such as fibroblast growth factor and Eph/ephrin pathways). Transcription factors were grouped according to their specific expression in enteric progenitor cells (such as MEF2C), enteric neurons (such as SOX4), or neuron subpopulations (such as SATB1 and SOX6). Lack of SOX6 in the ENS reduced the numbers of gastric dopamine neurons and delayed gastric emptying.ConclusionsUsing transcriptome and histochemical analyses of the developing mouse and human ENS, we mapped expression patterns of transcription and signaling factors. Further studies of these candidate determinants might elucidate the mechanisms by which enteric stem cells differentiate into neuronal subtypes and form distinct connectivity patterns during ENS development. We found expression of SOX6 to be required for development of gastric dopamine neurons.

Visual Neurons in the Superior Colliculus Innervated by Islet2+ or Islet2− Retinal Ganglion Cells Display Distinct Tuning Properties

Throughout the visual system, different subtypes of neurons are tuned to distinct aspects of the visual scene, establishing parallel circuits. Defining the mechanisms by which such tuning arises has been a long-standing challenge for neuroscience. To investigate this, we have focused on the retina’s projection to the superior colliculus (SC), where multiple visual neuron subtypes have been described. The SC receives inputs from a variety of retinal ganglion cell (RGC) subtypes; however, which RGCs drive the tuning of different SC neurons remains unclear. Here, we pursued a genetic approach that allowed us to determine the tuning properties of neurons innervated by molecularly defined subpopulations of RGCs. In homozygous Islet2-EphA3 knock-in (Isl2EA3/EA3) mice, Isl2+ and Isl2− RGCs project to non-overlapping sub-regions of the SC. Based on molecular and anatomic data, we show that significantly more Isl2− RGCs are direction-selective (DS) in comparison with Isl2+ RGCs. Targeted recordings of visual responses from each SC sub-region in Isl2EA3/EA3 mice revealed that Isl2− RGC-innervated neurons were significantly more DS than those innervated by Isl2+ RGCs. Axis-selective (AS) neurons were found in both sub-regions, though AS neurons innervated by Isl2+ RGCs were more tightly tuned. Despite this segregation, DS and AS neurons innervated by Isl2+ or Isl2− RGCs did not differ in their spatial summation or spatial frequency (SF) tuning. Further, we did not observe alterations in receptive field (RF) size or structure of SC neurons innervated by Isl2+ or Isl2− RGCs. Together, these data show that innervation by Isl2+ and Isl2− RGCs results in distinct tuning in the SC and set the stage for future studies investigating the mechanisms by which these circuits are built.

Age-Dependent Alpha-Synuclein Accumulation and Phosphorylation in the Enteric Nervous System in a Transgenic Mouse Model of Parkinson's Disease.

The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of α-synuclein (α-syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model. We found that the expression and accumulation of α-syn increased gradually in neurons of Meissner's and Auerbach's plexuses of the gastrointestinal tract with age (from 1 week to 2 years). In addition, α-syn was increasingly phosphorylated at the serine 129 residue, reflecting pathological alterations of the protein over time. Furthermore, α-syn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-α-Syn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis.

Chapter 2 - Signaling molecules of the CNS as targets of autoimmunity

Ion channels and receptors are the fundamental basis for neuronal communication in the nervous system and are important targets of autoimmunity. The different neuronal domains contain a unique repertoire of voltage-gated Na(+) (Nav), Ca(2+) (Cav), and K(+) (Kv), as well as other K(+) channels and hyperpolarization-gated cyclic nucleotide-regulated channels. The distinct ion channel distribution defines the electrophysiologic properties of different subtypes of neurons. The different neuronal compartments also express neurotransmitter-gated ion channels, or ionotropic receptors, as well as G protein-coupled receptors. Of particular relevance in the central nervous system are excitatory glutamate receptors and inhibitory γ-aminobutyric acid and glycine receptors. The interactions among different ion channels and receptors regulate neuronal excitability; frequency and pattern of firing of action potentials (AP); propagation of the AP along the axon; neurotransmitter release at synaptic terminals; AP backpropagation from the axon initial segment to the somatodendritic domain; dendritic integration of synaptic signals; and use-dependent plasticity.

Transcriptional control of neural crest specification into peripheral glia.

The neural crest is a transient migratory multipotent cell population that originates from the neural plate border and is formed at the end of gastrulation and during neurulation in vertebrate embryos. These cells give rise to many different cell types of the body such as chondrocytes, smooth muscle cells, endocrine cells, melanocytes, and cells of the peripheral nervous system including different subtypes of neurons and peripheral glia. Acquisition of lineage-specific markers occurs before or during migration and/or at final destination. What are the mechanisms that direct specification of neural crest cells into a specific lineage and how do neural crest cells decide on a specific migration route? Those are fascinating and complex questions that have existed for decades and are still in the research focus of developmental biologists. This review discusses transcriptional events and regulations occurring in neural crest cells and derived lineages, which control specification of peripheral glia, namely Schwann cell precursors that interact with peripheral axons and further differentiate into myelinating or nonmyelinating Schwann cells, satellite cells that remain tightly associated with neuronal cell bodies in sensory and autonomous ganglia, and olfactory ensheathing cells that wrap olfactory axons, both at the periphery in the olfactory mucosa and in the central nervous system in the olfactory bulb. Markers of the different peripheral glia lineages including intermediate multipotent cells such as boundary cap cells, as well as the functions of these specific markers, are also reviewed. Enteric ganglia, another type of peripheral glia, will not be discussed in this review. GLIA 2015;63:1883-1896.

Human Stem Cells and Surrogate Tissues for Basic and Translational Study of Mental Disorders

Human Stem Cells and Surrogate Tissues for Basic and Translational Study of Mental Disorders

MGluR5 promotes the differentiation of rat neural progenitor cells into cholinergic neurons and activation of extracellular signal-related protein kinases

Metabotropic glutamate receptors (mGluRs) regulate neurogenesis in the mammalian central nervous system during development and throughout adulthood. However, the mechanisms remain unknown. The present study was aimed at investigating the effect of mGluR5 on the differentiation of rat neural progenitor cells (NPCs) into neurons as well as the underlying molecular mechanisms. NPCs were treated with mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), mGluR5 siRNA, and antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride (MPEP), respectively. Three different subtypes of neurons (cholinergic, GABAergic, and dopaminergic neurons) were evaluated, and the activation of signaling pathways of mitogen-activated protein kinases was determined. Results showed that CHPG caused rat NPCs to differentiate into neurons, whereas mGluR5 siRNA and MPEP inhibited the cell differentiation. The proportion of cholinergic neurons increased with CHPG treatment and decreased after siRNA or MPEP treatment, whereas there were no significant changes in the proportions of GABAergic and dopaminergic neurons after treatment. The phosphorylated ERK1/2 levels increased after CHPG treatment and decreased after siRNA or MPEP treatment. In conclusion, our findings showed that mGluR5 caused rat NPCs to differentiate into cholinergic neurons by activating ERKs, suggesting that mGluR5 may play a significant role in the mechanism and treatment of degenerative diseases such as Alzheimer's disease.

Neurogenin2 expression together with NeuroM regulates GDNF family neurotrophic factor receptor α1 (GFRα1) expression in the embryonic spinal cord

In many regions of the nervous system, the combinatorial action of transcriptional factors specifies the individual fate of neuronal subtypes. Contrary to this, we report that a single transcriptional factor controls a phenotype shared by different subtypes of neurons, namely the expression of a neurotrophic factor receptor in the spinal cord. Along the dorsoventral axis of the chick embryo spinal cord, the expression pattern of a specific receptor for glial cell line derived-neurotrophic factor (GDNF family of receptors α1: GFRα1) was related to that of two basic helix-loop-helix (bHLH) transcriptional factors (NeuroM and Neurogenin2: Ngn2). In ovo electroporation in the chick embryo revealed that the overexpression of NeuroM alone was sufficient to induce ectopic GFRα1 expression without overt neuronal differentiation, whereas the suppression of NeuroM activity resulted in the specific loss of GFRα1 expression, indicating that NeuroM may act as a differentiation factor for GFRα1 expression. Ngn2 overexpression was also sufficient to induce precocious GFRα1 expression. However, the forced expression of both obligate suppressor and activator forms of Ngn2 also induced aberrant GFRα1 expression. Thus, any deviation from an optimum level of Ngn2 expression resulted in aberrant GFRα1 expression. Consistent with this, manipulation of Ngn2 expression levels by other bHLH factors also resulted in ectopic GFRα1 expression. For example, the downregulation by Ascl1 and the upregulation by Ptf1a induced ectopic GFRα1 expression, irrespective of endogenous expression patterns of Ascl1 and Ptf1a (Ascl1/Ptf1) in the spinal cord. The suppression of Ascl1/Ptf1a activities abolished Ngn2 and GFRα1 expression, even in Ascl1/Ptf1a-negative regions. These data indicate the presence of a distinct regulatory sequence for a determinant of GFRα1 expression, in which Ascl1/Ptf1a may competitively intervene to stochastically modulate default Ngn2 expression levels. Thus, Ngn2 together with NeuroM serves as readout to regulate GFRα1 expression, which occurs in multiple subtypes of spinal neurons.

Focus on Molecules: Math5 and retinal ganglion cells

The LIM-homeodomain transcription factor Islet-1 (Isl1) has been widely used as a marker of different subtypes of neurons in the developing and mature retina of vertebrates. During retinal neurogenesis, early Isl1 expression is detected in the nuclei of neuroblasts that give rise to ganglion, amacrine, bipolar, and horizontal cells. In the mature retina, Isl1 expression is restricted to the nuclei of ganglion cells, cholinergic amacrine cells, ON-bipolar cells, and subpopulations of horizontal cells. Recent studies have explored the functional mechanisms of Isl1 during specification and differentiation of these retinal cell types. Thus, conditional inactivation of Isl1 in the developing mouse retina disrupts retinal function, and also results in optic nerve hypoplasia, marked reductions in mature ganglion, amacrine, and bipolar cells, and a substantial increase in horizontal cells. Furthermore, conditional knockout shows delayed ganglion cell axon growth, ganglion cell axon guidance error, and ganglion cell nerve fiber defasciculation. These data together suggest a possible role for Isl1 in the early differentiation and maintenance of different vertebrate retinal cell types. This review examines whether the expression pattern of Isl1 during vertebrate retinal development is conserved across vertebrate species, and discusses current understanding of the developmental functions of Isl1 in retinogenesis.

Gradients of the Drosophila Chinmo BTB-Zinc Finger Protein Govern Neuronal Temporal Identity

Many neural progenitors, including Drosophila mushroom body (MB) and projection neuron (PN) neuroblasts, sequentially give rise to different subtypes of neurons throughout development. We identified a novel BTB-zinc finger protein, named Chinmo (Chronologically inappropriate morphogenesis), that governs neuronal temporal identity during postembryonic development of the Drosophila brain. In both MB and PN lineages, loss of Chinmo autonomously causes early-born neurons to adopt the fates of late-born neurons from the same lineages. Interestingly, primarily due to a posttranscriptional control, MB neurons born at early developmental stages contain more abundant Chinmo than their later-born siblings. Further, the temporal identity of MB progeny can be transformed toward earlier or later fates by reducing or increasing Chinmo levels, respectively. Taken together, we suggest that a temporal gradient of Chinmo (Chinmo(high) --> Chinmo(low)) helps specify distinct birth order-dependent cell fates in an extended neuronal lineage.

Chinmo and Neuroblast Temporal Identity

Although spatial patterning during embryonic development is well characterized, a corresponding framework for temporal patterning has not been established. In this issue, Zhu et al. (2006) identify the Chinmo protein as conferring temporal identity on the neural progeny of Drosophila neuroblasts, revealing appealing parallels with spatial patterning.