The Tale of the Three Brothers – Shh, Wnt, and Fgf during Development of the Thalamus

The thalamic complex is an essential part of the brain that requires a combination of specialized activities to attain its final complexity. In the following review we will describe the induction process of the mid-diencephalic organizer (MDO) where three different signaling pathways merge: Wnt, Shh, and Fgf. Here, we dissect the function of each signaling pathway in the thalamus in chronological order of their appearance. First we describe the Wnt mediated induction of the MDO and compartition of the caudal forebrain, then the Shh mediated determination of proneural gene expression before discussing recent progress in characterizing Fgf function during thalamus development. Then, we focus on transcription factors, which are regulated by these pathways and which play a pivotal role in neurogenesis in the thalamus. The three signaling pathways act together in a strictly regulated chronology to orchestrate the development of the entire thalamus

Neurogenesis in zebrafish – from embryo to adult

Neurogenesis in the developing central nervous system consists of the induction and proliferation of neural progenitor cells and their subsequent differentiation into mature neurons. External as well as internal cues orchestrate neurogenesis in a precise temporal and spatial way. In the last 20 years, the zebrafish has proven to be an excellent model organism to study neurogenesis in the embryo. Recently, this vertebrate has also become a model for the investigation of adult neurogenesis and neural regeneration. Here, we summarize the contributions of zebrafish in neural development and adult neurogenesis

Pax6 regulates the formation of the habenular nuclei by controlling the temporospatial expression of Shh in the diencephalon in vertebrates

The aim of this study was to describe epidemiologic characteristics of intestinal parasites in a population in south of Tehran, Iran. A retrospective cross-sectional study of patients with suspicious intestinal parasitic infections referred to the Zakaria Razi Laboratory in Shahre-Ray, southern Tehran, Iran, was conducted from April 21, 2004 to October 20, 2005. All stool samples were examined and socio-demographic informations were retrieved. Of 4,371 referred patients, 466 (239 males and 227 females) were laboratory diagnosed with intestinal parasites, with a period prevalence of 10.7. Blastocystis hominis (B. hominis) and Giardia lamblia (G. lamblia) were the most frequent intestinal parasites. More than half of patients aged � 18 years had a low level of educational attainment (e.g. illiterate, primary school, high school) (170/331, 54.1). Further, majority of patients were homemakers (42.3, 140/331) or workers (28.1, 93/331) employed in various business settings such as food industry and construction. Findings of this study showed that intestinal parasitic infections are still a major public health challenge in Iran that needs to be addressed. We believe that public education, improving sanitation conditions of underdeveloped areas/communities, community involvement, and supporting evidence-based practice/programs are the major keys to success in preventing the spread of intestinal parasitic infections in Iran

Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis

During embryogenesis, morphogens form a concentration gradient in responsive tissue, which is then translated into a spatial cellular pattern. The mechanisms by which morphogens spread through a tissue to establish such a morphogenetic field remain elusive. Here, we investigate by mutually complementary simulations and in vivo experiments how Wnt morphogen transport by cytonemes differs from typically assumed diffusion-based transport for patterning of highly dynamic tissue such as the neural plate in zebrafish. Stochasticity strongly influences fate acquisition at the single cell level and results in fluctuating boundaries between pattern regions. Stable patterning can be achieved by sorting through concentration dependent cell migration and apoptosis, independent of the morphogen transport mechanism. We show that Wnt transport by cytonemes achieves distinct Wnt thresholds for the brain primordia earlier compared with diffusion-based transport. We conclude that a cytoneme-mediated morphogen transport together with directed cell sorting is a potentially favored mechanism to establish morphogen gradients in rapidly expanding developmental systems

Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals

The thyroid is an endocrine gland in all vertebrates that develops from the ventral floor of the anterior pharyngeal endoderm. Unravelling the molecular mechanisms of thyroid development helps to understand congenital hypothyroidism caused by the absence or reduction of this gland in newborn humans. Severely reduced or absent thyroid-specific developmental genes concomitant with the complete loss of the functional gland in the zebrafish hands off (han, hand2) mutant reveals the han gene as playing a novel, crucial role in thyroid development. han-expressing tissues surround the thyroid primordium throughout development. Fate mapping reveals that, even before the onset of thyroid-specific developmental gene expression, thyroid precursor cells are in close contact with han-expressing cardiac lateral plate mesoderm. Grafting experiments show that han is required in surrounding tissue, and not in a cell-autonomous manner, for thyroid development. Loss of han expression in the branchial arches and arch-associated cells after morpholino knock-down of upstream regulator genes does not impair thyroid development, indicating that other han-expressing structures, most probably cardiac mesoderm, are responsible for the thyroid defects in han mutants. The zebrafish ace (fgf8) mutant has similar thyroid defects as han mutants, and chemical suppression of fibroblast growth factor (FGF) signalling confirms that this pathway is required for thyroid development. FGF-soaked beads can restore thyroid development in han mutants, showing that FGFs act downstream of or in parallel to han. These data suggest that loss of FGF-expressing tissue in han mutants is responsible for the thyroid defects

Lhx2 and Lhx9 Determine Neuronal Differentiation and Compartition in the Caudal Forebrain by Regulating Wnt Signaling

Initial axial patterning of the neural tube into forebrain, midbrain, and hindbrain primordia occurs during gastrulation. After this patterning phase, further diversification within the brain is thought to proceed largely independently in the different primordia. However, mechanisms that maintain the demarcation of brain subdivisions at later stages are poorly understood. In the alar plate of the caudal forebrain there are two principal units, the thalamus and the pretectum, each of which is a developmental compartment. Here we show that proper neuronal differentiation of the thalamus requires Lhx2 and Lhx9 function. In Lhx2/Lhx9-deficient zebrafish embryos the differentiation process is blocked and the dorsally adjacent Wnt positive epithalamus expands into the thalamus. This leads to an upregulation of Wnt signaling in the caudal forebrain. Lack of Lhx2/Lhx9 function as well as increased Wnt signaling alter the expression of the thalamus specific cell adhesion factor pcdh10b and lead subsequently to a striking anterior-posterior disorganization of the caudal forebrain. We therefore suggest that after initial neural tube patterning, neurogenesis within a brain compartment influences the integrity of the neuronal progenitor pool and border formation of a neuromeric compartment