RESUMEN

The plains vizcacha, Lagostomus maximus, is a precocial hystricomorph rodent with a gyrencephalic brain. This work aimed to perform a time-lapse analysis of the embryonic brain cortical development in the plains vizcacha to establish a species-specific temporal window for corticogenesis and the gyrencephaly onset. Additionally, a comparative examination with evolutionarily related rodents was conducted. Embryos from 40 embryonic days (ED) until the end of pregnancy ( ∼ $\sim $ 154 ED) were evaluated. The neuroanatomical examination determined transverse sulci at 80 ED and rostral lateral and caudal intraparietal sulci around 95 ED. Histological examination of corticogenesis showed emergence of the subplate at 43 ED and expansion of the subventricular zone (SVZ) and its division into inner and outer SVZs around 54 ED. The neocortical layers formation followed an inside-to-outside spatiotemporal gradient beginning with the emergence of layers VI and V at 68 ED and establishing the final six neocortical layers around 100 ED. A progressive increment of gyrencephalization index (GI) from 1.005 ± 0.003 around 70 ED, which reflects a smooth cortex, up to 1.07 ± 0.009 at the end of gestation, reflecting a gyrencephalic neuroanatomy, was determined. Contrarily, the minimum cortical thickness (MCT) progressively decreased from 61 ED up to the end of gestation. These results show that the decrease in the cortical thickness, which enables the onset of neocortical invaginations, occurs together with the expansion and subdivision of the SVZ. The temporal comparison of corticogenesis in plains vizcacha with that in relative species reflects a prenatal long process compared with other rodents that may give an evolutionary advantage to L. maximus as a precocial species.

Asunto(s)

Corteza Cerebral , Roedores , Animales , Corteza Cerebral/crecimiento & desarrollo , Roedores/anatomía & histología , Femenino , Embarazo , Neurogénesis/fisiología , Neocórtex/crecimiento & desarrollo

RESUMEN

Congenital Zika syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with a Brazilian ZIKV isolate and found that they were born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction in PH3+ cells, intermediate progenitor cells, and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV-infected cultures show a reduction in callosal axon length. GFAP labeling showed that an in utero infection compromises glial cells responsible for midline axon guidance. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis, but also axon guidance and growth across the midline.

Asunto(s)

Microcefalia , Malformaciones del Sistema Nervioso , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Embarazo , Femenino , Humanos , Animales , Ratones , Cuerpo Calloso , Malformaciones del Sistema Nervioso/etiología , Neurogénesis

RESUMEN

The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex.

Asunto(s)

Movimiento Celular/fisiología , Corteza Cerebral , Histona Demetilasas/metabolismo , Factor de Empalme Asociado a PTB/metabolismo , Células Piramidales/fisiología , Factores de Edad , Animales , Animales Recién Nacidos , Línea Celular , Movimiento Celular/genética , Corteza Cerebral/citología , Corteza Cerebral/embriología , Corteza Cerebral/crecimiento & desarrollo , Proteínas de Dominio Doblecortina , Electroporación , Embrión de Mamíferos , Regulación del Desarrollo de la Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/fisiología , Histona Demetilasas/genética , Proteínas de Homeodominio/metabolismo , Antígeno Ki-67/metabolismo , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Neuropéptidos/metabolismo , Proteínas Nucleares/metabolismo , Factor de Empalme Asociado a PTB/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proteínas Represoras/metabolismo , Factores de Transcripción SOXB1/metabolismo

RESUMEN

[This corrects the article on p. 67 in vol. 10, PMID: 27013978.].

RESUMEN

The central nervous system areas displaying the highest structural and functional complexity correspond to the so called cortices, i.e., concentric alternating neuronal and fibrous layers. Corticogenesis, i.e., the development of the cortical organization, depends on the temporal-spatial organization of several developmental events: (a) the duration of the proliferative phase of the neuroepithelium, (b) the relative duration of symmetric (expansive) versus asymmetric (neuronogenic) sub phases, (c) the spatial organization of each kind of cell division, (e) the time of determination and cell cycle exit and (f) the time of onset of the post-mitotic neuronal migration and (g) the time of onset of the neuronal structural and functional differentiation. The first five events depend on molecular mechanisms that perform a fine tuning of the proliferative activity. Changes in any of them significantly influence the cortical size or volume (tangential expansion and radial thickness), morphology, architecture and also impact on neuritogenesis and synaptogenesis affecting the cortical wiring. This paper integrates information, obtained in several species, on the developmental roles of cell proliferation in the development of the optic tectum (OT) cortex, a multilayered associative area of the dorsal (alar) midbrain. The present review (1) compiles relevant information on the temporal and spatial organization of cell proliferation in different species (fish, amphibians, birds, and mammals), (2) revises the main molecular events involved in the isthmic organizer (IsO) determination and localization, (3) describes how the patterning installed by IsO is translated into spatially organized neural stem cell proliferation (i.e., by means of growth factors, receptors, transcription factors, signaling pathways, etc.) and (4) describes the morpho- and histogenetic effect of a spatially organized cell proliferation in the above mentioned species. A brief section on the OT evolution is also included. This section considers how the differential operation of cell proliferation could explain differences among species.

RESUMEN

Los microRNA son RNA pequeños no codificantes que regulan la traducción de RNA mensajeros. En el tejido cerebral de mamífero, existe una regulación temporal de los niveles de estas moléculas durante el desarrollo, los cuales están relacionados directamente con momentos específicos en la formación del sistema nervioso central y tienen un papel trascendental en la citoarquitectura cerebral. Existe una gran cantidad de deficiencias y/o alteraciones de las funciones cerebrales que no pueden ser explicadas por causas genéticas o detectadas por los métodos convencionales, por lo que es de gran importancia identificar marcadores moleculares no invasivos de problemas sutiles relacionados con alteraciones en la diferenciación, proliferación, muerte celular u organización del tejido nervioso que puedan tener consecuencias negativas en la vida postnatal del producto, principalmente en el área cognitiva, motora y social. Una alternativa es la búsqueda y determinación de los niveles de microRNA involucrados en la corticogénesis fetal en suero materno. Aquí revisaremos algunas de las características de estas moléculas que las hacen buenas candidatas para ser consideradas como biomarcadores del desarrollo cerebral fetal, entre las que se encuentran la forma en que se sintetizan y llegan al torrente sanguíneo, su estabilidad, su patrón de expresión durante la corticogénesis y su presencia en el suero materno.

---

MicroRNAs are small non-coding RNAs that regulate the translation of messenger RNA into proteins. During the development of the mammalian brain tissue, there is a temporal regulation of the levels of these molecules, which are directly related to specific stages in the formation of the central nervous system; microRNAs play a major role in brain cytoarchitecture. There are multiple alterations in brain function that cannot be explained by genetic causes or detected by conventional methods; for this reason, it is very important to identify molecules that can be proposed as biomarkers in a noninvasive way for pathologies related to alterations upon cell differentiation, proliferation and death or brain tissue organization that may have negative consequences in postnatal life and that can potentially lead to cognitive, motor and social deficits. An alternative is determining the microRNA levels involved in fetal corticogenesis in the maternal serum. In this article, we review some characteristics of these molecules that make them candidates to be proposed as biomarkers of fetal brain development, such as the pathway throught which they are synthesized and released into the bloodstream, their stability, their expression pattern during corticogenesis and their presence in the maternal serum.