RESUMEN
cGAS-STING signalling is induced by detection of foreign or mislocalised host double-stranded (ds)DNA within the cytosol. STING acts as the major signalling hub, where it controls production of type I interferons and inflammatory cytokines. Basally, STING resides on the ER membrane. Following activation STING traffics to the Golgi to initiate downstream signalling and subsequently to endolysosomal compartments for degradation and termination of signalling. While STING is known to be degraded within lysosomes, the mechanisms controlling its delivery remain poorly defined. Here we utilised a proteomics-based approach to assess phosphorylation changes in primary murine macrophages following STING activation. This identified numerous phosphorylation events in proteins involved in intracellular and vesicular transport. We utilised high-temporal microscopy to track STING vesicular transport in live macrophages. We subsequently identified that the endosomal complexes required for transport (ESCRT) pathway detects ubiquitinated STING on vesicles, which facilitates the degradation of STING in murine macrophages. Disruption of ESCRT functionality greatly enhanced STING signalling and cytokine production, thus characterising a mechanism controlling effective termination of STING signalling.
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Inmunidad Innata , Proteínas de la Membrana , Ratones , Animales , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Transducción de Señal/fisiología , Macrófagos/metabolismo , Nucleotidiltransferasas/metabolismo , ADN , Complejos de Clasificación Endosomal Requeridos para el Transporte/genéticaRESUMEN
Helicobacter pylori encodes homologues of PilM, PilN and PilO from bacteria with Type IV pili, where these proteins form a pilus alignment complex. Inactivation of pilO changes H. pylori motility in semi-solid media, suggesting a link to the chemosensory pathways or flagellar motor. Here, we showed that mutation of the pilO or pilN gene in H. pylori strain SS1 reduced the mean linear swimming speed in liquid media, implicating PilO and PilN in the function, or regulation of, the flagellar motor. We also demonstrated that the soluble variants of H. pylori PilN and PilO share common biochemical properties with their Type IV pili counterparts which suggests their adapted function in the bacterial flagellar motor may be similar to that in the Type IV pili.
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The middle temporal (MT) area of the extrastriate visual cortex has long been studied in adulthood for its distinctive physiological properties and function as a part of the dorsal stream, yet interestingly it possesses a similar maturation profile as the primary visual cortex (V1). Here, we examined whether an early-life lesion in MT of marmoset monkeys (six female, two male) altered the dorsal stream development and the behavioral precision of reaching-to-grasp sequences. We observed permanent changes in the anatomy of cortices associated with both reaching (parietal and medial intraparietal areas) and grasping (anterior intraparietal area), as well as in reaching-and-grasping behaviors. In addition, we observed a significant impact on the anatomy of V1 and the direction sensitivity of V1 neurons in the lesion projection zone. These findings indicate that area MT is a crucial node in the development of primate vision, affecting both V1 and areas in the dorsal visual pathway known to mediate visually guided manual behaviors.SIGNIFICANCE STATEMENT Previous studies have identified a role for the MT area of the visual cortex in perceiving motion, yet none have examined its central role in the development of the visual cortex and in the establishment of visuomotor behaviors. To address this, we used a unilateral MT lesion model in neonatal marmosets before examining the anatomic, physiological, and behavioral consequences. In adulthood, we observed perturbations in goal-orientated reach-and-grasp behavior, altered direction selectivity of V1 neurons, and changes in the cytoarchitecture throughout dorsal stream areas. This study highlights the importance of MT as a central node in visual system development and consequential visuomotor activity.
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Percepción de Movimiento/fisiología , Desempeño Psicomotor/fisiología , Corteza Visual/fisiología , Vías Visuales/fisiología , Percepción Visual/fisiología , Animales , Callithrix , Femenino , Masculino , Neuronas/fisiología , Estimulación Luminosa , Corteza Visual/diagnóstico por imagen , Vías Visuales/diagnóstico por imagenRESUMEN
The medial pulvinar (PM) is a multimodal associative thalamic nucleus, recently evolved in primates. PM participates in integrative and modulatory functions, including directed attention, and consistently exhibits alterations in disorders such as schizophrenia and autism. Despite essential cognitive functions, the cortical inputs to the PM have not been systematically investigated. To date, less than 20 cortices have been demonstrated to project to PM. The goal of this study was to establish a comprehensive map of the cortical afferents to PM in the marmoset monkey. Using a magnetic resonance imaging-guided injection approach, we reveal 62 discrete cortices projecting to the adult marmoset PM. We confirmed previously reported connections and identified further projections from discrete cortices across the temporal, parietal, retrosplenial-cingulate, prefrontal, and orbital lobes. These regions encompass areas recipient of PM efferents, demonstrating the reciprocity of the PM-cortical connectivity. Moreover, our results indicate that PM neurones projecting to distinct cortices are intermingled and form multimodal cell clusters. This microunit organization, believed to facilitate cross-modal integration, contrasts with the large functional subdivisions usually observed in thalamic nuclei. Altogether, we provide the first comprehensive map of PM cortical afferents, an essential stepping stone in expanding our knowledge of PM and its function.
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Corteza Cerebral/fisiología , Vías Nerviosas/fisiología , Pulvinar/fisiología , Tálamo/fisiología , Animales , Callithrix/fisiología , Macaca mulatta , Masculino , Núcleos Talámicos/fisiologíaRESUMEN
An evolutionary hallmark of anthropoid primates, including humans, is the use of vision to guide precise manual movements. These behaviors are reliant on a specialized visual input to the posterior parietal cortex. Here, we show that normal primate reaching-and-grasping behavior depends critically on a visual pathway through the thalamic pulvinar, which is thought to relay information to the middle temporal (MT) area during early life and then swiftly withdraws. Small MRI-guided lesions to a subdivision of the inferior pulvinar subnucleus (PIm) in the infant marmoset monkey led to permanent deficits in reaching-and-grasping behavior in the adult. This functional loss coincided with the abnormal anatomical development of multiple cortical areas responsible for the guidance of actions. Our study reveals that the transient retino-pulvinar-MT pathway underpins the development of visually guided manual behaviors in primates that are crucial for interacting with complex features in the environment.
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Callithrix/fisiología , Fuerza de la Mano/fisiología , Pulvinar/fisiología , Vías Visuales/fisiología , Animales , Animales Recién Nacidos , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Masculino , Neuronas/fisiología , Lóbulo Parietal/anatomía & histología , Lóbulo Parietal/fisiologíaRESUMEN
The current model, based on rodent data, proposes that thalamocortical afferents (TCA) innervate the subplate towards the end of cortical neurogenesis. This implies that the laminar identity of cortical neurons is specified by intrinsic instructions rather than information of thalamic origin. In order to determine whether this mechanism is conserved in the primates, we examined the growth of thalamocortical (TCA) and corticofugal afferents in early human and monkey fetal development. In the human, TCA, identified by secretagogin, calbindin, and ROBO1 immunoreactivity, were observed in the internal capsule of the ventral telencephalon as early as 7-7.5 PCW, crossing the pallial/subpallial boundary (PSB) by 8 PCW before the calretinin immunoreactive corticofugal fibers do. Furthermore, TCA were observed to be passing through the intermediate zone and innervating the presubplate of the dorsolateral cortex, and already by 10-12 PCW TCAs were occupying much of the cortex. Observations at equivalent stages in the marmoset confirmed that this pattern is conserved across primates. Therefore, our results demonstrate that in primates, TCAs innervate the cortical presubplate at earlier stages than previously demonstrated by acetylcholinesterase histochemistry, suggesting that pioneer thalamic afferents may contribute to early cortical circuitry that can participate in defining cortical neuron phenotypes.
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Corteza Cerebral/embriología , Neuronas Aferentes/citología , Tálamo/embriología , Vías Aferentes/citología , Vías Aferentes/embriología , Vías Aferentes/metabolismo , Animales , Callithrix , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Humanos , Neuronas Aferentes/metabolismo , Roedores , Tálamo/citología , Tálamo/metabolismoRESUMEN
Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder of childhood. It is primarily characterised by high levels of activity, inattention, and impulsivity, and has strong negative impacts on academic functioning. Children with ADHD show a reduction in volume, and hypoactivity, in a range of brain regions. The underlying mechanisms behind these phenotypes are unknown, however, variants in several genes with known roles in neurodevelopment are associated with ADHD. In this review we discuss how these ADHD associated genes contribute to neurodevelopment, and how variants in these genes could give rise to the neurological phenotypes seen in ADHD.
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Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/etiología , Encéfalo/fisiopatología , Humanos , Conducta Impulsiva , Trastornos del Neurodesarrollo/genética , Neuronas/fisiología , Sinapsis/genética , Sinapsis/fisiologíaRESUMEN
The pulvinar is primarily referred to for its role in visual processing. However, the 'visual pulvinar' only encompasses the inferior and lateral regions of this complex thalamic nucleus. The remaining medial portion (medial pulvinar, PM) establishes distinct cortical connectivity and has been associated with directed attention, executive functions and working memory. These functions are particularly impaired in neurodevelopmental disorders, including schizophrenia and attention deficit and hyperactivity disorder (ADHD), both of which have been associated with abnormal PM architecture and connectivity. With these disorders becoming more prevalent in modern societies, we review the literature to better understand how the PM can participate in the pathophysiology of cognitive disorders and how a better understanding of the development and function of this thalamic nucleus, which is most likely exclusive to the primate brain, can advance clinical research and treatments.
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Trastornos del Neurodesarrollo/etiología , Pulvinar/fisiología , Animales , Evolución Biológica , Humanos , Pulvinar/embriologíaRESUMEN
The visual cortex is organized into discrete domains characterized by their specific function, connectivity, chemoarchitecture, and cytoarchitecture. Gradients of transcription factors across the anteroposterior and mediolateral axes of the neocortex have previously been demonstrated to specify the main sensory regions. However, they do not account for the establishment of multiple areas in the primate visual cortex, which occupies approximately 50% of the neocortical surface. We demonstrate that the guidance molecule Semaphorin3A (Sema3A) is initially secreted in the cortical plate of the embryonic marmoset monkey and acts as an intrinsic cue to control the migration of subpopulations of neuronal progenitors and projection neurons expressing the receptor Neuropilin 1 (Npn1). During the first 2 postnatal weeks, Sema3A expression becomes primarily associated with ventral visual cortical areas, leading to the specific migration of Npn1+ neurons in the late maturing visual areas. In the mouse, Sema3A distribution is not arealized, but Npn1 expression becomes restricted to the posterior neocortex at embryonic day 16.5. The selective reduction in the striate cortex we observe in Sema3A-/- animals potentially results from the differential distribution of Npn1+ cells. Therefore, the Sema3A/Npn1 pathway participates to the parcellation of the visual neocortex in both the mouse and the marmoset, however, through different regulatory processes.
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Neocórtex/citología , Neocórtex/fisiología , Neuronas/metabolismo , Semaforina-3A/metabolismo , Factores de Edad , Animales , Animales Recién Nacidos , Callithrix , Embrión de Mamíferos , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuropilina-1/genética , Neuropilina-1/metabolismo , ARN Mensajero/metabolismo , Semaforina-3A/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Ephs form the largest family of receptor tyrosine kinases. They interact with the membrane-bound ligands - ephrins - to control crucial aspects of brain development. EphA4 is the most prominent member of the family in terms of versatility and ability to bind most ephrin ligands. EphA4 regulates brain development by modulating neuronal migration and connectivity. In the present study, we address the involvement of EphA4 in patterning the primary visual cortex (V1) of the marmoset monkey by characterizing the cellular expression profile of EphA4 from late embryonic stages to adulthood. We identified continuous expression on neurons in the cortical plate and mature neocortical layers, similar to that described in the mouse, excluding a role for EphA4 in the formation of borders between visual areas in the marmoset neocortex. In addition to neurons, we also report expression of EphA4 on glial populations, including radial glia and astrocytes. In contrast to what is seen in the mouse, EphA4 expression on astrocytes persists in the adult marmoset V1, including around blood vessels and in the white matter. Robust expression by glial populations, which retain neurogenic properties in the postnatal marmoset, indicates that EphA4 may have acquired additional roles during evolution, with important implications for the benefits of EphA4-blocking therapies following brain injury.
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Neuroglía/metabolismo , Neuronas/metabolismo , Receptor EphA4/metabolismo , Corteza Visual/enzimología , Corteza Visual/crecimiento & desarrollo , Animales , Callithrix , Femenino , Masculino , RatonesRESUMEN
The primate prefrontal cortex (PFC) is a quintessential hub of cognitive functions. Amidst its intricate neural architecture, the interplay of distinct neuronal subtypes, notably parvalbumin (PV) and somatostatin (SST) interneurons (INs), emerge as a cornerstone in sculpting cortical circuitry and governing cognitive processes. While considerable strides have been made in elucidating the developmental trajectory of these neurons in rodent models, our understanding of their postmigration developmental dynamics in primates still needs to be studied. Disruptions to this developmental trajectory can compromise IN function, impairing signal gating and circuit modulation within cortical networks. This study examined the expression patterns of PV and SST, ion transporter KCC2, and ion channel subtypes Kv3.1b, and Nav1.1 - associated with morphophysiological stages of development in the postnatal marmoset monkey in different frontal cortical regions (granular areas 8aD, 8aV, 9, 46; agranular areas 11, 47L). Our results demonstrate that the maturation of PV+ INs extends into adolescence, characterized by discrete epochs associated with specific expression dynamics of ion channel subtypes. Interestingly, we observed a postnatal decrease in SST interneurons, contrasting with studies in rodents. This endeavor broadens our comprehension of primate cortical development and furnishes invaluable insights into the etiology and pathophysiology of neurodevelopmental disorders characterized by perturbations in PV and SST IN function.
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The bacterial flagellar motor is a molecular nanomachine, the assembly and regulation of which requires many accessory proteins. Their identity, structure and function are often discovered through characterisation of mutants with impaired motility. Here, we demonstrate the functional association of the Helicobacter pylori peptidoglycan-associated lipoprotein (HpPal) with the flagellar motor by analysing the motility phenotype of the ∆pal mutant, and present the results of the preliminary X-ray crystallographic analysis of its globular C-terminal domain HpPal-C. Purified HpPal-C behaved as a dimer in solution. Crystals of HpPal-C were grown by the hanging drop vapour diffusion method using medium molecular weight polyethylene glycol (PEG) Smear as the precipitating agent. The crystals belong to the primitive orthorhombic space group P1 with unit cell parameters a = 50.7, b = 63.0, c = 75.1 Å. X-ray diffraction data were collected to 1.8 Å resolution on the Australian Synchrotron beamline MX2. Calculation of the Matthews coefficient (VM=2.24 Å3/Da) and molecular replacement showed that the asymmetric unit contains two protein subunits. This study is an important step towards elucidation of the non-canonical role of H. pylori Pal in the regulation, or function of, the flagellar motor.
Asunto(s)
Helicobacter pylori , Helicobacter pylori/química , Proteínas Bacterianas/metabolismo , Peptidoglicano/metabolismo , Australia , Cristalografía por Rayos X , Lipoproteínas/química , Lipoproteínas/metabolismoRESUMEN
Molecular cloning techniques enabling contemporaneous expression of two or more protein-coding sequences provide an invaluable tool for understanding the molecular regulation of cellular functions. The Cre-lox system is used for inducing the expression of recombinant proteins encoded within a bi-/poly-cistronic cassette. However, leak expression of transgenes is often observed in the absence of Cre recombinase activity, compromising the utility of this approach. To investigate the mechanism of leak expression, we generated Cre-inducible bi-cistronic vectors to monitor the expression of transgenes positioned either 5' or 3' of a 2A peptide or internal ribosomal entry site (IRES) sequence. Cells transfected with these bi-cistronic vectors exhibited Cre-independent leak expression specifically of transgenes positioned 3' of the 2A peptide or IRES sequence. Similarly, AAV-FLEX vectors encoding bi-cistronic cassettes or fusion proteins revealed the selective Cre-independent leak expression of transgenes positioned at the 3' end of the open reading frame. Our data demonstrate that 5' transgenes confer promoter-like activity that drives the expression of 3' transgenes. An additional lox-STOP-lox cassette between the 2A sequence and 3' transgene dramatically decreased Cre-independent transgene expression. Our findings highlight the need for appropriate experimental controls when using Cre-inducible bi-/poly-cistronic constructs and inform improved design of vectors for more tightly regulated inducible transgene expression.
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The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.
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Corteza Prefontal Dorsolateral , Evolución Molecular , Primates , Somatostatina , Tirosina 3-Monooxigenasa , Adulto , Animales , Dopamina/metabolismo , Corteza Prefontal Dorsolateral/citología , Corteza Prefontal Dorsolateral/metabolismo , Humanos , Pan troglodytes , Primates/genética , Análisis de la Célula Individual , Somatostatina/genética , Somatostatina/metabolismo , Transcriptoma , Tirosina 3-Monooxigenasa/genética , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Infants and adults respond differently to brain injuries. Specifically, improved neuronal sparing along with reduced astrogliosis and glial scarring often observed earlier in life, likely contributes to improved long-term outcomes. Understanding the underlying mechanisms could enable the recapitulation of neuroprotective effects, observed in infants, to benefit adults after brain injuries. We reveal that in primates, Eph/ ephrin signaling contributes to age-dependent reactive astrocyte behavior. Ephrin-A5 expression on astrocytes was more protracted in adults, whereas ephrin-A1 was only expressed on infant astrocytes. Furthermore, ephrin-A5 exacerbated major hallmarks of astrocyte reactivity via EphA2 and EphA4 receptors, which was subsequently alleviated by ephrin-A1. Rather than suppressing reactivity, ephrin-A1 signaling shifted astrocytes towards GAP43+ neuroprotection, accounting for improved neuronal sparing in infants. Reintroducing ephrin-A1 after middle-aged focal ischemic injury significantly attenuated glial scarring, improved neuronal sparing and preserved circuitry. Therefore, beneficial infant mechanisms can be recapitulated in adults to improve outcomes after CNS injuries.
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Astrocitos , Lesiones Encefálicas , Envejecimiento , Animales , Encéfalo/patología , Lesiones Encefálicas/patología , Cicatriz/patología , Efrina-A1 , Efrina-A5 , Gliosis/patologíaRESUMEN
Vascular endothelial growth factor C (VEGF-C) was first identified as a regulator of the vascular system, where it is required for the development of lymphatic vessels. Here we report actions of VEGF-C in the central nervous system. We detected the expression of the VEGF-C receptor VEGFR-3 in neural progenitor cells in Xenopus laevis and mouse embryos. In Xenopus tadpole VEGF-C knockdowns and in mice lacking Vegfc, the proliferation of neural progenitors expressing VEGFR-3 was severely reduced, in the absence of intracerebral blood vessel defects. In addition, Vegfc-deficient mouse embryos showed a selective loss of oligodendrocyte precursor cells (OPCs) in the embryonic optic nerve. In vitro, VEGF-C stimulated the proliferation of OPCs expressing VEGFR-3 and nestin-positive ventricular neural cells. VEGF-C thus has a new, evolutionary conserved function as a growth factor selectively required by neural progenitor cells expressing its receptor VEGFR-3.
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Encéfalo/embriología , Diferenciación Celular/fisiología , Factores de Crecimiento Nervioso/metabolismo , Neuronas/metabolismo , Células Madre/metabolismo , Factor C de Crecimiento Endotelial Vascular/metabolismo , Animales , Encéfalo/citología , Encéfalo/metabolismo , Células Cultivadas , Evolución Molecular , Proteínas de Filamentos Intermediarios/metabolismo , Larva , Ventrículos Laterales/citología , Ventrículos Laterales/embriología , Ventrículos Laterales/metabolismo , Ratones , Ratones Noqueados , Ratones Transgénicos , Proteínas del Tejido Nervioso/metabolismo , Nestina , Neuronas/citología , Oligodendroglía/citología , Oligodendroglía/metabolismo , Nervio Óptico/citología , Nervio Óptico/embriología , Nervio Óptico/metabolismo , Ratas , Ratas Wistar , Células Madre/citología , Factor C de Crecimiento Endotelial Vascular/genética , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo , Xenopus laevisRESUMEN
Rodent models, particularly mice, have dominated the field of developmental neuroscience for decades, like they have in most fields of biomedicine research. However, with 80 million years since rodents and primates last shared a common ancestor, the use of mice to model the development of the human brain is not without many shortcomings. The human brain diverges from the mouse brain in many aspects and is comprised of novel structures as well as diversified cellular subtypes. While these newly evolved features have no equivalent in rodents, they are observed in nonhuman primates. Therefore, elucidating the cellular mechanisms underlying the development and maturation of the healthy and diseased human brain can be achieved using less complex nonhuman primates. Historically, macaques were the preferred nonhuman primate model. However, over the past decade, the New World marmoset monkey (Callithrix jacchus) has gained more importance, particularly in the field of neurodevelopment. With its small size, twin or triplet birth, and prosocial behavior, the marmoset is an ideal model to study normal brain development as well as neurodevelopmental disorders, which are often associated with abnormal social behaviors. The growing interest in the marmoset has prompted many comparative studies, all demonstrating that the marmoset brain closely resembles that of the human and is perfectly suited to model human brain development. The marmoset is thus poised to extend its influence in the field of neurodevelopment and will hopefully fill the gaps that the mouse has left in our understanding of how our brain forms and how neurodevelopmental disorders originate.
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Encéfalo , Callithrix , Animales , Humanos , Macaca , RatonesRESUMEN
Recent evidence demonstrates that the pulvinar nuclei play a critical role in shaping the connectivity and function of the multiple cortical areas they connect. Surprisingly, however, little is known about the development of this area, the largest corpus of the thalamic nuclei, which go on to occupy 40% of the adult thalamus in the human. It was proposed that the nonhuman primate and the human pulvinar develop according to very different processes, with a greatly reduced neurogenic period in nonhuman primate compared to human and divergent origins. In the marmoset monkey, we demonstrate that neurons populating the pulvinar are generated throughout gestation, suggesting that this aspect of development is more similar to the human than first predicted. While we were able to confirm the diencephalic source of pulvinar neurons, we provide new evidence contesting the presence of an additional niche in the telencephalon. Finally, our study defines new molecular markers that will simplify future investigations in the development and evolution of the pulvinar.
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Callithrix/fisiología , Pulvinar/crecimiento & desarrollo , Acetilcolinesterasa/metabolismo , Animales , Animales Recién Nacidos , Proliferación Celular , Diencéfalo/embriología , Diencéfalo/crecimiento & desarrollo , Femenino , Regulación de la Expresión Génica , Inmunohistoquímica , Neurogénesis/fisiología , Neuronas/fisiología , Embarazo , Pulvinar/citología , Pulvinar/embriología , Tercer Ventrículo/citología , Tercer Ventrículo/embriología , Vías Visuales/fisiologíaRESUMEN
Throughout evolution, the neocortex has undergone a dramatic expansion providing the substrate for increasingly complex cognitive abilities, culminating with humans. The enlargement of the neocortex did not affect its' basic organization, which is remarkably conserved from rodents to primates. The mouse has thus proven an advantageous model to decipher the molecular and cellular mechanisms supporting neocortical development. However, it is of limited benefit when studying the mechanisms leading to the inclusion of higher order association areas, which form the largest fraction of the primate neocortex. In the quest for a suitable nonhuman primate model to study the developmental mechanism of neocortical patterning and expansion, researchers focussed on the Old World macaque, routinely employed in functional and behavioral studies. However, the species has many limitations making studies difficult and/or impractical. Therefore, in the past couple of decades, the New World common marmoset (Callithrix jacchus) has drawn much attention and become an accepted model. The marmoset has the advantage of a smooth neocortical sheet, enabling the direct correspondence between developing cortices and the comprehensive map established for the adult, with a significant amount of cortical maturation occurring during the postnatal period. This review presents the contributions of recent marmoset studies to our understanding of the mechanisms regulating corticogenesis in a complex species, the molecular control of neocortical patterning and the sequential maturation of visual cortical areas while commenting on the future of the species in the field. Furthermore, while these new findings are relevant to developmental biology, in order to understand how new cortical areas have emerged to expand cognitive abilities, they also represent a foundation for the better understanding of developmental cognitive disorders. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 263-272, 2017.