Acquisition of the Midbrain Dopaminergic Neuronal Identity

The mesodiencephalic dopaminergic (mdDA) group of neurons comprises molecularly distinct subgroups, of which the substantia nigra (SN) and ventral tegmental area (VTA) are the best known, due to the selective degeneration of the SN during Parkinson’s disease. However, although significant research has been conducted on the molecular build-up of these subsets, much is still unknown about how these subsets develop and which factors are involved in this process. In this review, we aim to describe the life of an mdDA neuron, from specification in the floor plate to differentiation into the different subsets. All mdDA neurons are born in the mesodiencephalic floor plate under the influence of both SHH-signaling, important for floor plate patterning, and WNT-signaling, involved in establishing the progenitor pool and the start of the specification of mdDA neurons. Furthermore, transcription factors, like Ngn2, Ascl1, Lmx1a, and En1, and epigenetic factors, like Ezh2, are important in the correct specification of dopamine (DA) progenitors. Later during development, mdDA neurons are further subdivided into different molecular subsets by, amongst others, Otx2, involved in the specification of subsets in the VTA, and En1, Pitx3, Lmx1a, and WNT-signaling, involved in the specification of subsets in the SN. Interestingly, factors involved in early specification in the floor plate can serve a dual function and can also be involved in subset specification. Besides the mdDA group of neurons, other systems in the embryo contain different subsets, like the immune system. Interestingly, many factors involved in the development of mdDA neurons are similarly involved in immune system development and vice versa. This indicates that similar mechanisms are used in the development of these systems, and that knowledge about the development of the immune system may hold clues for the factors involved in the development of mdDA neurons, which may be used in culture protocols for cell replacement therapies

Molecular Organization and Patterning of the Medulla Oblongata in Health and Disease

The medulla oblongata, located in the hindbrain between the pons and the spinal cord, is an important relay center for critical sensory, proprioceptive, and motoric information. It is an evolutionarily highly conserved brain region, both structural and functional, and consists of a multitude of nuclei all involved in different aspects of basic but vital functions. Understanding the functional anatomy and developmental program of this structure can help elucidate potential role(s) of the medulla in neurological disorders. Here, we have described the early molecular patterning of the medulla during murine development, from the fundamental units that structure the very early medullary region into 5 rhombomeres (r7–r11) and 13 different longitudinal progenitor domains, to the neuronal clusters derived from these progenitors that ultimately make-up the different medullary nuclei. By doing so, we developed a schematic overview that can be used to predict the cell-fate of a progenitor group, or pinpoint the progenitor domain of origin of medullary nuclei. This schematic overview can further be used to help in the explanation of medulla-related symptoms of neurodevelopmental disorders, e.g., congenital central hypoventilation syndrome, Wold–Hirschhorn syndrome, Rett syndrome, and Pitt–Hopkins syndrome. Based on the genetic defects seen in these syndromes, we can use our model to predict which medullary nuclei might be affected, which can be used to quickly direct the research into these diseases to the likely affected nuclei

Black Pete through the eyes of Dutch children

The traditional figure of Black Pete seen during the December festivities around Sinterklaas (the Dutch Santa Claus) in the Netherlands has sparked fierce debates about his racial stereotypical characteristics and his potentially negative effects on children’s opinions about black people. The Black Pete phenomenon has even been discussed by the United Nations Committee on the Elimination of Racial Discrimination, resulting in a report urging the Netherlands to eliminate this form of racial stereotyping. The adult debate about Black Pete is clearly important, but Sinterklaas is essentially a children’s holiday. Surprisingly, there have never been any systematic studies to examine children’s views on Black Pete. The current study is the first to do so. In a sample of 201 children aged 5–7 years, we collected free descriptions of Black Pete, asked children to group him in relation to other figures, and to assign characteristics to him and comparison figures. The results showed that (1) Children are clearly aware of Black Pete’s skin color and subordinate status; (2) Children associate Black Pete more with clowns than with black people; (3) Children evaluate Black Pete very positively, but the positive characteristics do not generalize to their evaluation of black people. The findings illustrate the deep-rooted childhood origins of many Dutch people’s affection for Black Pete and their lack of awareness of his relation to racial stereotypes. This explains the resistance to changing the Black Pete figure and the slowness of the change process on this front.Development Psychopathology in context: famil

Multi-processor system-level synthesis for multiple applications on platform fpga

ABSTRACT Multiprocessor systems-on-chip (MPSoC) are being developed in increasing numbers to support the high number of applications running on modern embedded systems. Designing and programming such systems prove to be a major challenge. Most of the current design methodologies rely on creating the design by hand, and are therefore error-prone and time-consuming. This also limits the number of design points that can be explored. While some efforts have been made to automate the flow and raise the abstraction level, these are still limited to single-application designs. In this paper, we present a design methodology to generate and program MPSoC designs in a systematic and automated way for multiple applications. The architecture is automatically inferred from the application specifications, and customized for it. The flow is ideal for fast design space exploration (DSE) in MPSoC systems. We present results of a case study to compute the buffer-throughput trade-offs in real-life applications, H263 and JPEG decoders. The generation of the entire project takes about 100ms, and the whole DSE was completed in 45 minutes, including the FPGA mapping and synthesis

<i>Nkx2.9</i> Contributes to Mid-Hindbrain Patterning by Regulation of mdDA Neuronal Cell-Fate and Repression of a Hindbrain-Specific Cell-Fate

Nkx2.9 is a member of the NK homeobox family and resembles Nkx2.2 both in homology and expression pattern. However, while Nkx2.2 is required for development of serotonergic neurons, the role of Nkx2.9 in the mid-hindbrain region is still ill-defined. We have previously shown that Nkx2.9 expression is downregulated upon loss of En1 during development. Here, we determined whether mdDA neurons require Nkx2.9 during their development. We show that Nkx2.9 is strongly expressed in the IsO and in the VZ and SVZ of the embryonic midbrain, and the majority of mdDA neurons expressed Nkx2.9 during their development. Although the expression of Dat and Cck are slightly affected during development, the overall development and cytoarchitecture of TH-expressing neurons is not affected in the adult Nkx2.9-depleted midbrain. Transcriptome analysis at E14.5 indicated that genes involved in mid- and hindbrain development are affected by Nkx2.9-ablation, such as Wnt8b and Tph2. Although the expression of Tph2 extends more rostral into the isthmic area in the Nkx2.9 mutants, the establishment of the IsO is not affected. Taken together, these data point to a minor role for Nkx2.9 in mid-hindbrain patterning by repressing a hindbrain-specific cell-fate in the IsO and by subtle regulation of mdDA neuronal subset specification