The developing optic tectum: An asymmetrically organized system and the need for a redefinition of the notion of sensitive period.

The present article summarizes the main events involved in the isthmic organizer and optic tectum determination and analyses how optic tectum patterning is translated, by the organized operation of several specific cell behaviors, into the terminally differentiated optic tectum. The paper proposes that this assembling of temporally/spatially organized cell behaviors could be incorporated into a wider notion of patterning and that, given the asymmetric organization of the developing optic tectum, the notion of "sensitive period" does not capture the whole complexity of midbrain development and the pathogenesis of congenital disorders. The cell behaviors involved in the optic tectum development are organized in time and space by the isthmic organizer.

NGF, TrkA-P and neuroprotection after a hypoxic event in the developing central nervous system.

A decrease in the concentration of oxygen in the blood and tissues (hypoxia) produces important, sometimes irreversible, damages in the central nervous system (CNS) both during development and also postnatally. The present work aims at analyzing the expression of nerve growth factor (NGF) and p75 and the activation of TrkA in response to an acute normobaric hypoxic event and to evaluate the possible protective role of exogenous NGF. The developing chick optic tectum (OT), a recognized model of corticogenesis, was used as experimental system by means of in vivo and in vitro studies.

Corrigendum: Morphogenetic and Histogenetic Roles of the Temporal-Spatial Organization of Cell Proliferation in the Vertebrate Corticogenesis as Revealed by Inter-specific Analyses of the Optic Tectum Cortex Development.

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

Morphogenetic and Histogenetic Roles of the Temporal-Spatial Organization of Cell Proliferation in the Vertebrate Corticogenesis as Revealed by Inter-specific Analyses of the Optic Tectum Cortex Development.

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.

Temporal-spatial correlation between angiogenesis and corticogenesis in the developing chick optic tectum.

The developing chick optic tectum is a widely used model of corticogenesis and angiogenesis. Cell behaviors involved in corticogenesis and angiogenesis share several regulatory mechanisms. In this way the 3D organizations of both systems adapt to each other.

uPA-uPAR molecular complex is involved in cell signaling during neuronal migration and neuritogenesis.

Background: In the development of the central nervous system (CNS), neuronal migration and neuritogenesis are crucial processes for establishing functional neural circuits. This relies on the regulation exerted by several signaling molecules, which play important roles in axonal growth and guidance. The urokinase-type plasminogen activator (uPA)-in association with its receptor-triggers extracellular matrix proteolysis and other cellular processes through the activation of intracellular signaling pathways.

Sonic hedgehog (Shh)/Gli modulates the spatial organization of neuroepithelial cell proliferation in the developing chick optic tectum.

Background: Sonic hedgehog (Shh)/Gli pathway plays an important regulatory role on the neuroepithelial cells (NEc) proliferation in the dorsal regions of the developing vertebrate Central Nervous System. The aim of this paper was to analyze the effect of the Shh/Gli signaling pathway activation on the proliferation dynamics and/or the spatial organization of the NEc proliferation activity during early stages of the developing chick optic tectum (OT). In ovo pharmacological gain and loss of hedgehog function approaches were complemented with in vivo electroporation experiments in order to create ectopic sources of either Shh or Gli activator (GliA) proteins in the OT.

EphA3 expressed in the chicken tectum stimulates nasal retinal ganglion cell axon growth and is required for retinotectal topographic map formation.

Background: Retinotopic projection onto the tectum/colliculus constitutes the most studied model of topographic mapping and Eph receptors and their ligands, the ephrins, are the best characterized molecular system involved in this process. Ephrin-As, expressed in an increasing rostro-caudal gradient in the tectum/colliculus, repel temporal retinal ganglion cell (RGC) axons from the caudal tectum and inhibit their branching posterior to their termination zones. However, there are conflicting data regarding the nature of the second force that guides nasal axons to invade and branch only in the caudal tectum/colliculus.

Optic tectum morphogenesis: a step-by-step model based on the temporal-spatial organization of the cell proliferation. Significance of deterministic and stochastic components subsumed in the spatial organization.

Background: Cell proliferation plays an important morphogenetic role. This work analyzes the temporal-spatial organization of cell proliferation as an attempt to understand its contribution to the chick optic tectum (OT) morphogenesis.

Results: A morphogenetic model based on space-dependent differences in cell proliferation is presented.

The chick optic tectum developmental stages. A dynamic table based on temporal- and spatial-dependent histogenetic changes: A structural, morphometric and immunocytochemical analysis.

Development is often described as temporal sequences of developmental stages (DSs). When tables of DS are defined exclusively in the time domain they cannot discriminate histogenetic differences between different positions along a spatial reference axis. We introduce a table of DSs for the developing chick optic tectum (OT) based on time- and space-dependent changes in quantitative morphometric parameters, qualitative histogenetic features and immunocytochemical pattern of several developmentally active molecules (Notch1, Hes5, NeuroD1, β-III-Tubulin, synaptotagmin-I and neurofilament-M).

Acute hypoxia differentially affects the NMDA receptor NR1, NR2A and NR2B subunit mRNA levels in the developing chick optic tectum: stage-dependent plasticity in the 2B-2A ratio.

It is known that the NMDA-R NR1 subunit is needed for the receptor activity and that under hypoxia the evolution toward apoptosis or neuronal survival depends on the balance NR2A/NR2B subunits. This paper analyzes the effect of acute hypoxia on the above mentioned subunits mRNAs during development. The mean percentage of NR1+ neurons displayed the higher plasticity during development while the NR2A+ neurons the higher stability.

Brachytherapy versus radical hysterectomy after external beam chemoradiation: a non-randomized matched comparison in IB2-IIB cervical cancer patients.

Background: A current paradigm in the treatment of cervical cancer with radiation therapy is that intracavitary brachytherapy is an essential component of radical treatment. This is a matched retrospective comparison of the results of treatment in patients treated with external beam chemoradiation (EBRT-CT) and radical hysterectomy versus those treated with identical chemoradiation followed by brachytherapy.

Methods: In this non-randomized comparison EBRT-CT protocol was the same in both groups of 40 patients.

Acute hypoxia differentially affects the gamma-aminobutyric acid type A receptor alpha(1), alpha(2), beta(2), and gamma(2) subunit mRNA levels in the developing chick optic tectum: stage-dependent sensitivity.

This investigation analyzes the effect of an acute hypoxic treatment on the level of four (alpha(1), alpha(2), beta(2), and gamma(2)) subunit mRNAs of the GABA(A) receptor in layer "i" of the developing chick optic tectum. Our results show that 1 hr of normobaric acute hypoxia significantly changes the subunit mRNA levels. Different subunit mRNAs display different sensitivity to hypoxia: alpha(1), beta(2), and gamma(2) mRNAs are highly sensitive, whereas alpha(2) mRNA is almost not affected.

Developmental pattern of NADPH-diaphorase positive neurons in chick optic tectum is sensitive to changes in visual stimulation.

The chick retinotectal system is a suitable model to investigate the mechanisms involved in the establishment of synaptic connections in whose refinement nitric oxide was implicated. The purpose of this work was to describe the developmental pattern of the nitric oxide synthase (NOS)-positive neurons as well as to determine if it is sensitive to changes in visual stimulation. The NADPH-diaphorase histochemical method was used to describe and quantify NOS neurons in normally stimulated and subnormally stimulated chickens.

Tissue-type plasminogen activator activity in morphologically normal tissues adjacent to gastrointestinal carcinomas is associated with the degree of tumor progression.

Purpose: To investigate whether the level of plasminogen activator (PA) activity assayed in gastrointestinal carcinomas and the "morphologically normal tissues" adjacent to them is associated with the degree of tumor progression.

Methods: Tumor and "normal tissues" were obtained from gastrointestinal surgical samples to assess urokinase-type (u-PA) and tissue-type plasminogen activator (t-PA) activities by radial caseinolytic assay and the expression of PA inhibitor-1 (PAI-1) by ELISA. We compared the PA system between the tumor and "normal tissues" and we investigated the existence of correlations between: (a) PA production in the tumor and "normal tissues", (b) different components of the PA system, and (c) PA system and the degree of tumor progression.

Development and localisation of GABA(A) receptor alpha1, alpha2, beta2 and gamma2 subunit mRNA in the chick optic tectum.

An in situ hybridisation technique was used to analyse the spatial and temporal pattern of expression of the mRNA encoding the four gamma-aminobutyric acid A (GABA(A)) receptor subunits (alpha1, alpha2, beta2, and gamma2) in the developing chick optic tectum. As a rule, layer i, layer h, and transient cell compartment 3 (TCC3) show the highest levels of expression, especially of alpha1, alpha2 and beta2, which undergo striking changes as a function of time. Apart from these common features, the global pattern is highly complex and dynamic.

Developmental changes in the spatial pattern of mesencephalic trigeminal nucleus (Mes5) neuron populations in the developing chick optic tectum.

The developing mesencephalic trigeminal nucleus (nucleus of the fifth cranial nerve; Mes5) is composed of four neuron populations: 1) the medial group, located at the tectal commissure; 2) the lateral group distributed along the optic tectum hemispheres; 3) a group outside the neural tube; and 4) a population located at the posterior commissure. The present work aims to elucidate the site of appearance, temporal evolution, and spatial distribution of the four Mes5 populations during development. According to detailed qualitative observations Mes5 neurons appear as a primitive unique population along a thin dorsal medial band of the mesencephalon.

The formation of intercellular junctions in insect stem cell progeny (cockroach intestinal epithelium).

The stages in the development of intercellular junctions have been followed in the mesenteric caecal cells of the cockroach midgut, where two types of mature cell, the columnar and the secretory, exist. 'Nests' of undifferentiated replacement cells occur at intervals along the basal lamina, consisting of central, dividing cells and peripheral semi-lunar cells; the former act as proliferative stem cells to give rise to either pre-columnar or pre-secretory cells. The semi-lunar cells are pre-columnar and produce an attenuated process which gradually projects up to the luminal surface, producing microvilli and a dense extracellular substance en route.