Cerebral cortex | EPFL Graph Search

The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of allocortex. It is separated into two cortices, by the longitudinal fissure that divides the cerebrum into the left and right cerebral hemispheres. The two hemispheres are joined beneath the cortex by the corpus callosum. The cerebral cortex is the largest site of neural integration in the central nervous system. It plays a key role in attention, perception, awareness, thought, memory, language, and consciousness. The cerebral cortex is part of the brain responsible for cognition. In most mammals, apart from small mammals that have small brains, the cerebral cortex is folded, providing a greater surface area in the confined volume of the cranium. Apart from minimising brain and cranial volume, cortical folding is crucial fo

From the early steps of whisker formation to its evolutionary disappearance: the (curious) case of Prdm1 and its regulation

Pierluigi Giuseppe Manti

Whiskers (also known as vibrissae) are sensory organs that are thought to have first appeared in Therapsida, a group of synapsids that includes mammals and evolutionary ancestors like the Thrinaxodon(1). They are highly conserved among mammals to the notable exception of the higher primates and are important for behavior, especially for nocturnal animals and the ones living in burrows(2). Furthermore, the mechanoreceptors of the vibrissae signal to the primary somatosensory cortex, where a discrete and well-defined structure in layer 4 represents each whisker(3). This structure, known as barrel cortex, occupies a large portion of the rodent brain. Strikingly, Prdm1 conditional KO (cKO) mice are one of the rare transgenic strains that do not develop whiskers while forming a pelage; on the other hand, the other head structures expressing Prdm1 (including pelage hair follicles and teeth) grow normally(4). In the developing whisker pad, Prdm1 expression is confined to the mesenchyme underlying the embryonic epidermis that will later form the whisker epidermal placode; it lasts until dermal papilla formation, when a âswitchâ occurs to the precursors of the inner root sheath. The Prdm1 ablation study we conducted revealed the absence of the patterned up-regulation of Bmp2 (marker of placode formation), Shh (a protein secreted by the epidermal placode responsible for the first epidermal signal) and Bmp4 (expressed in the pre-follicle mesenchyme). On the other hand, Lef1 is expressed uniformly in the mesenchyme of the whisker pad, thus pointing out the integrity of the Î²Catenin-mediated first mesenchymal signal. Those results suggest the role of Prdm1 as a master gene in whisker development. Prdm1 expressing cells are mainly non-proliferative; however, a small subpopulation at the periphery is cycling. Being Sox2 coexpressed with Prdm1 in the whisker mesenchyme, we performed lineage tracing with Sox2CreERT2 and ROSAYFP transgenic strains. Those experiments revealed that Sox2/Prdm1 expressing cells contribute to the formation of the dermal papilla, dermal sheath and putative pericytes of the whisker follicle and thus constitute a population of embryonic progenitors crucial for whisker formation. We subsequently investigated the development of the barrel cortex in our cKO mice. Intriguingly, a disorganized pattern was observed in cKO mice, suggesting that the loss of expression of a single gene, and consequently the disappearance of vibrissae, drastically impacts the development of the whole somatosensory system. Finally, we hypothesized that the loss of Prdm1 expression might explain the disappearance of whisker follicles in the human during evolution. Prdm1 being no longer expressed in the human lineage during hair follicle development(5), we reasoned that the loss of regulatory elements of its upstream genes might contribute to this phenomenon; we demonstrated that Lef1 acts upstream of Prdm1 during whisker development and are currently testing the role of its potential enhancers (Leaf) during this process. Bibliography: 1: (http://en.wikipedia.org/wiki/therapsid) 2: Petersen, C. C. H. The Functional Organization of the Barrel Cortex. Neuron 56, 339â355 (2007) 3: Woolsey, T. A. & Van der Loos, H. The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res. 17, 205â242 (1970) 4: Robertson, E. J. et al. Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice. Development 134, 4335â4345 (2007). 5: Sellheyer, K. & Krahl, D. Blimp-1: a marker of terminal differentiation but not of sebocytic progenitor cells. J. Cutan. Pathol. 37, 362â370 (2010).

EPFL2016

Molecular heterogeneity of the ganglionic eminence and its relationship to the birth of neocortical interneurons

Susan Willi Monnerat

Neocortical function and malfunction depends critically on a spectrum of inhibitory interneurons. To gain novel insight in normal brain function and mechanisms leading to diseases, such as epilepsy or schizophrenia, the knowledge about the specific functions of each interneuron type appears crucial. To date, the mystery about the diversity of neocortical interneurons remains still unresolved, even though much effort was devoted to the characterization of mature interneurons in the neocortex. Ten years ago, the discovery of the ganglionic eminence (GE) as origin of neocortical interneurons allowed a novel approach to assess their various identities, and thus prompted researchers to follow the fate of cells accommodated in this region. Despite the knowledge of the source location and its subdivision into three GEs, their molecular identity remained unknown apart from few genes, and consequently unabled the specific isolation of precursor cells. To this purpose, we performed extensive microarray analysis of the three GEs at various developmental timepoints to reveal their molecular heterogeneity and identify novel precursor cell surface markers that would enable their prospective isolation by flow cytometry and subsequent fate assessment in vitro and in vivo. Surprisingly, molecular heterogeneity of the three GEs was restricted to few differentially expressed genes. However, the differences in gene expression became more apparent at late developmental stage that may reflect the increased specification during development. Among the three GEs, the LGE and CGE resembled molecularly each other most, while the MGE and CGE were most distantly related to each other. Furthermore, our genome-wide expression study suggested that the CGE, a structure of so far controversial nature, was rather a unique structure than a fusion of the MGE and LGE. Analysis across developmental timepoints revealed that the MGE underwent tremendous changes in gene expression when compared to the differential expression existing between the homochronic MGE and cerebral cortex. In our microarray screen, we could identify Boc as a novel marker of LGE/CGE-resident precursor cells. Taking advantage of Boc that encodes a cell surface molecule, we could isolate the Boc+ cells from the GE by flow cytometry, and demonstrate that in contrast to Boc– cells, they self-renewed and differentiated into oligodendrocytes, astrocytes, and neurons, and thus identify them as progenitor cells. Furthermore, immunohistochemical studies suggested that Boc+ GE cells may correspond to radial glia, the embryonic neural stem cells. The specific expression of Boc in the LGE and CGE, but not in the MGE during their entire lifetime suggested that Boc is a reliable marker for LGE/CGE-resident precursor cells. To assess the fate of Boc+ GE cells, we performed homotypic transplantations of Boc+ and Boc– cells onto organotypic slice cultures, and observed that in contrast to Boc– cells, Boc+ cells did not migrate from the GE to the neocortex suggesting that Boc+ precursor cells of the GE do not generate neocortical interneurons. In future, additional fate-mapping studies of Boc+ GE cells, such as in vivo transplantation, should shed more light on the ability of Boc+ LGE/CGE precursor cells to generate neocortical interneurons, and dependent on the outcome serve to construct a cell-lineage tree of neocortical interneurons. Thus, Boc will remain a useful tool to investigate developmental processes underlying the generation of neocortical and/or other neurons, such as striatal neurons.

EPFL2007