Populational heterogeneity and partial migratory origin of the ventromedial hypothalamic nucleus: genoarchitectonic analysis in the mouse.

The ventromedial hypothalamic nucleus (VMH) is one of the most distinctive hypothalamic tuberal structures, subject of numerous classic and modern functional studies. Commonly, the adult VMH has been divided in several portions, attending to differences in cell aggregation, cell type, connectivity, and function. Consensus VMH partitions in the literature comprise the dorsomedial (VMHdm), and ventrolateral (VMHvl) subnuclei, which are separated by an intermediate or central (VMHc) population (topographic names based on the columnar axis).

Neurogenetic Heterochrony in Chick, Lizard, and Rat Mapped with Wholemount Acetylcholinesterase and the Prosomeric Model.

In the developing brain, the phenomenon of neurogenesis is manifested heterotopically, that is, much the same neurogenetic steps occur at different places with a different timetable. This is due apparently to early molecular regionalization of the neural tube wall in the anteroposterior and dorsoventral dimensions, in a checkerboard pattern of more or less deformed quadrangular histogenetic areas. Their respective fate is apparently specified by a locally specific combination of active/repressed genes known as "molecular profile.

Molecular Segmentation of the Spinal Trigeminal Nucleus in the Adult Mouse Brain.

The trigeminal column is a hindbrain structure formed by second order sensory neurons that receive afferences from trigeminal primary (ganglionic) nerve fibers. Classical studies subdivide it into the principal sensory trigeminal nucleus located next to the pontine nerve root, and the spinal trigeminal nucleus which in turn consists of oral, interpolar and caudal subnuclei. On the other hand, according to the prosomeric model, this column would be subdivided into segmental units derived from respective rhombomeres.

Sim1-expressing cells illuminate the origin and course of migration of the nucleus of the lateral olfactory tract in the mouse amygdala.

We focus this report on the nucleus of the lateral olfactory tract (NLOT), a superficial amygdalar nucleus receiving olfactory input. Mixed with its Tbr1-expressing layer 2 pyramidal cell population (NLOT2), there are Sim1-expressing cells whose embryonic origin and mode of arrival remain unclear. We examined this population with Sim1-ISH and a Sim1-tauLacZ mouse line.

Salient brain entities labelled in P2rx7-EGFP reporter mouse embryos include the septum, roof plate glial specializations and circumventricular ependymal organs.

The purinergic system is one of the oldest cell-to-cell communication mechanisms and exhibits relevant functions in the regulation of the central nervous system (CNS) development. Amongst the components of the purinergic system, the ionotropic P2X7 receptor (P2X7R) stands out as a potential regulator of brain pathology and physiology. Thus, P2X7R is known to regulate crucial aspects of neuronal cell biology, including axonal elongation, path-finding, synapse formation and neuroprotection.

A radial histogenetic model of the mouse pallial amygdala.

Conventional anatomic models of the rodent (mammalian) amygdala are based on section planes oblique to its intrinsic radial glial organization. As a result, we still lack a model of amygdalar histogenesis in terms of radial units (progenitor domains and related radial migration and layering patterns). A radial model of the mouse pallial amygdala is first offered here, based on three logical steps: (1) analysis of amygdalar radial structure in variously discriminative genoarchitectonic material, using an optimal ad hoc section plane; (2) testing preliminary models with experiments labelling at the brain surface single packets of radial glia processes, to be followed into the ventricular surface across intervening predicted elements; (3) selection of 81 differential amygdalar gene markers and checking planar and radial aspects of their distribution across the model elements.

LacZ-reporter mapping of Dlx5/6 expression and genoarchitectural analysis of the postnatal mouse prethalamus.

We present here a thorough and complete analysis of mouse P0-P140 prethalamic histogenetic subdivisions and corresponding nuclear derivatives, in the context of local tract landmarks. The study used as fundamental material brains from a transgenic mouse line that expresses LacZ under the control of an intragenic enhancer of Dlx5 and Dlx6 (Dlx5/6-LacZ). Subtle shadings of LacZ signal, jointly with pan-DLX immunoreaction, and several other ancillary protein or RNA markers, including Calb2 and Nkx2.

Concentric ring topology of mammalian cortical sectors and relevance for patterning studies.

Models aiming to explain causally the evolutionary or ontogenetic emergence of the pallial isocortex and its regional/areal heterogeneity in mammals use simple or complex assumptions about the pallial structure present in basal mammals and nonmammals. The question arises: how complex is the pattern that needs to be accounted for in causal models? This topic is also paramount for comparative purposes, since some topological relationships may be explained as being ancestral, rather than newly emerged. The mouse pallium is apt to be reexamined in this context, due to the breadth of available molecular markers and correlative experimental patterning results.

The Postmigratory Alar Topography of Visceral Cranial Nerve Efferents Challenges the Classical Model of Hindbrain Columns.

The classic columnar model of cranial nerve central representation assumes that all motor and sensory hindbrain neurons develop within four radial migration domains, held to be separated by a sulcal alar-basal boundary (sulcus limitans). This essay reviews a number of developmental data that challenge these concepts. These results are interpreted within the framework of present day neuromeric conception of the brainstem (the prosomeric model).

An exercise in brain genoarchitectonics: Analysis of AZIN2-Lacz expressing neuronal populations in the mouse hindbrain.

We examined in detail the distribution of AZIN2 (antizyme inhibitor 2) expression in the adult mouse hindbrain and neighboring spinal cord. AZIN2, similar to previously known AZIN1, is a recently-discovered, a functional paralog of ornithine decarboxylase (ODC). Due to their structural similarity to ODC, both AZIN1 and AZIN2 counteract the inhibitory action of 3 known antizymes (AZ1-3) on the ODC synthesis of polyamines, thus increasing intracytoplasmic levels of polyamines.

Selective early expression of the orphan nuclear receptor Nr4a2 identifies the claustrum homolog in the avian mesopallium: Impact on sauropsidian/mammalian pallium comparisons.

The transcription factor Nr4a2 was recently revealed as a very early developmental marker of the claustrum (CL) proper in the mouse. The earliest claustral primordium was identified superficially, dorsal to the olfactory cortex, and was subsequently covered by the Nr4a2-negative cells of the insular cortex. Some tangentially migrating claustral derivatives (subplate cells and some endopiriform elements) also expressed this marker.

Radial and tangential migration of telencephalic somatostatin neurons originated from the mouse diagonal area.

The telencephalic subpallium is the source of various GABAergic interneuron cohorts that invade the pallium via tangential migration. Based on genoarchitectonic studies, the subpallium has been subdivided into four major domains: striatum, pallidum, diagonal area and preoptic area (Puelles et al. 2013; Allen Developing Mouse Brain Atlas), and a larger set of molecularly distinct progenitor areas (Flames et al.

Regionalized differentiation of CRH, TRH, and GHRH peptidergic neurons in the mouse hypothalamus.

According to the updated prosomeric model, the hypothalamus is subdivided rostrocaudally into terminal and peduncular parts, and dorsoventrally into alar, basal, and floor longitudinal zones. In this context, we examined the ontogeny of peptidergic cell populations expressing Crh, Trh, and Ghrh mRNAs in the mouse hypothalamus, comparing their distribution relative to the major progenitor domains characterized by molecular markers such as Otp, Sim1, Dlx5, Arx, Gsh1, and Nkx2.1.

Development of the serotonergic cells in murine raphe nuclei and their relations with rhombomeric domains.

The raphe nuclei represent the origin of central serotonergic projections. The literature distinguishes seven nuclei grouped into rostral and caudal clusters relative to the pons. The boundaries of these nuclei have not been defined precisely enough, particularly with regard to developmental units, notably hindbrain rhombomeres.

Distal-less-like protein distribution in the larval lamprey forebrain.

A polyclonal antibody against the Drosophila distal-less (DLL) protein, cross-reactive with cognate vertebrate proteins, was employed to map DLL-like expression in the midlarval lamprey forebrain. This work aimed to characterize in detail the separate diencephalic and telencephalic DLL expression domains, in order to test our previous modified definition of the lamprey prethalamus [Pombal and Puelles (1999) J Comp Neurol 414:391-422], adapt our earlier schema of prosomeric subdivisions in the lamprey forebrain to more recent versions of this model [Pombal et al. (2009) Brain Behav Evol 74:7-19] and reexamine the pallio-subpallial regionalization of the lamprey telencephalon.

Genoarchitectonic profile of developing nuclear groups in the chicken pretectum.

Earlier results on molecularly coded progenitor domains in the chicken pretectum revealed an anteroposterior subdivision of the pretectum in precommissural (PcP), juxtacommissural (JcP), and commissural (CoP) histogenetic areas, each specified differentially (Ferran et al. [2007] J Comp Neurol 505:379-403). Here we examined the nuclei derived from these areas with regard to characteristic gene expression patterns and gradual histogenesis (eventually, migration patterns).

Expression of antizyme inhibitor 2 in male haploid germinal cells suggests a role in spermiogenesis.

Recently, we have found that the antizyme inhibitor 2, a novel member of the antizyme binding proteins related to polyamine metabolism, was expressed mainly in the adult testes, although its function in testicular physiology is completely unknown. Therefore, in the present work, the spatial and temporal expression of antizyme inhibitor 2, and other genes related to polyamine metabolism were studied in the mouse testis, in an attempt to understand the role of antizyme inhibitor 2 in testicular functions. For that purpose, the temporal expression of different genes, during the first wave of spermatogenesis in postnatal mice, was studied by real-time RT-PCR, and the spatial distribution of transcripts and protein in the adult testis was examined by both RNA in situ hybridization and immunocytochemistry.

Early pretectal gene expression pattern shows a conserved anteroposterior tripartition in mouse and chicken.

A changing network of gene activity settles the molecular basis of regionalization in the nervous system. As a consequence, analysis of combined gene expressions patterns represents a powerful initial approach to decode the complex process that drives neurohistogenesis and generates distinct morphological features. We have started to do a comparative screening of molecular regionalization in the mouse and chicken pretectal region at selected developmental stages.

Conserved pattern of OTP-positive cells in the paraventricular nucleus and other hypothalamic sites of tetrapods.

The paraventricular nucleus complex (Pa) is a component of central neural circuitry that regulates several homeostatic variables. The paraventricular nucleus is composed of magnocellular neurons that project to the posterior pituitary and parvicellular neurons that project to numerous sites in the central nervous system. According to the revised prosomeric model, the paraventricular nucleus is located caudal to the eye stalk along the rostrocaudal dimension of the dorsal hypothalamic alar plate.

Lbx1 acts as a selector gene in the fate determination of somatosensory and viscerosensory relay neurons in the hindbrain.

Distinct types of relay neurons in the hindbrain process somatosensory or viscerosensory information. How neurons choose between these two fates is unclear. We show here that the homeobox gene Lbx1 is essential for imposing a somatosensory fate on relay neurons in the hindbrain.

Chicken lateral septal organ and other circumventricular organs form in a striatal subdomain abutting the molecular striatopallidal border.

The avian lateral septal organ (LSO) is a telencephalic circumventricular specialization with liquor-contacting neurons (Kuenzel and van Tienhoven [1982] J. Comp. Neurol.

Anatomical and gene expression mapping of the ventral pallium in a three-dimensional model of developing human brain.

Combining gene expression data with morphological information has revolutionized developmental neuroanatomy in the last decade. Visualization and interpretation of complex images have been crucial to these advances in our understanding of mechanisms underlying early brain development, as most developmental processes are spatially oriented, in topologically invariant patterns that become overtly distorted during brain morphogenesis. It has also become clear that more powerful methodologies are needed to accommodate the increasing volume of data available and the increasingly sophisticated analyses that are required, for example analyzing anatomy and multiple gene expression patterns at individual developmental stages, or identifying and analyzing homologous structures through time and/or between species.

A distinct preisthmic histogenetic domain is defined by overlap of Otx2 and Pax2 gene expression in the avian caudal midbrain.

Correlative in situ hybridization of Otx2, Pax2, Gbx2, and Fgf8 mRNA probes in adjacent serial sections through the chicken midbrain and isthmus at early to intermediate stages of development served to map in detail the area of overlap of Otx2 and Pax2 transcripts in the caudal midbrain. The neuronal populations developing within this preisthmic domain made up a caudal part of the midbrain reticular formation, the interfascicular nucleus, and the magnocellular (pre)isthmic nucleus, plus the corresponding part of the periaqueductal gray. The torus semicircularis-the inferior colliculus homolog-expressed Otx2 in its ventricular lining exclusively, but it never expressed Pax2.

3 dimensional modelling of early human brain development using optical projection tomography.

Background: As development proceeds the human embryo attains an ever more complex three dimensional (3D) structure. Analyzing the gene expression patterns that underlie these changes and interpreting their significance depends on identifying the anatomical structures to which they map and following these patterns in developing 3D structures over time. The difficulty of this task greatly increases as more gene expression patterns are added, particularly in organs with complex 3D structures such as the brain.

Gbx2 expression in the late embryonic chick dorsal thalamus.

The expression pattern of the transcription factor gene Gbx2 in the forebrain of chicken embryos (embryonic day 14) was mapped using digoxigenin-labeled riboprobes and compared with the expression of the transcription factors Pax6 and Nkx2.2. The topographic analysis of Gbx2 expression on coronal and sagittal sections discriminated the positions and boundaries of diverse neuronal nuclei belonging to the dorsal thalamus from neighboring territories (the epithalamus, ventral thalamus, pretectum, and the underlying basal plate).