Neurobiologia (secondo esonero)

Nervous System Beginnings

Gastrulation (provides a morphologic shape to the embryo), thanks to this morphogenetic process, produces 3 cell layers:

• Ectoderm (outside)
• Mesoderm (middle)
• Endoderm (inside)

Gastrulation (when the 3 layers forms) also forms the notocord (a rod-shaped structure made of mesoderm cells).

• Above the notocord lies the ectoderm that gives rise to the nervous system (neuroectoderm)
• The notochord also sends signals to make certain neuroectodermal cells become neural precursor cells, a process called neurulation or neural induction.

Neurulation signalling molecules:

• It requires like Bond morphogenetic process (BMP), Wnt, retinoic acid, Sonic Hedgehog, and fibroma grow factor (FGF) are all important signaling molecules for neurulation.
• The neuroectoderm cells exposed to these signals thicken into the neural plate on approx. day 16 of development.
• Part of the ectodermal layer form the neural plate, this is an active process that accounts signaling molecules that are

provides by ectoderm

Nervous System Formation- The neural plate folds inward to generate the neural tube on approx. day 21. This is the “primordium” of the brain & spinal cord.- The neural tube contains neuroblasts, which will generate neurons and glial cells

Neural Crest-The cells at the dorsal (“top”) part of the neural tube are called the neural crest cells. These cells form the basis for sensory relay neurons to the thalamus.- At the ventral (“bottom”) portion is the floorplate. These cells form primary motor neurons sent to the muscles.

Neural ProliferationAfter the neural tube is formed, the developing nervous system cells rapidly increase in number. Cell division occurs in the ventricular zone of the neural tube; when they leave the cell division cycle, cells migrate into other layers.

Cell divisionThe wall neural tube that is full of cells, they are quite large cell they are called neuroepitilial cells. When this cells approached cell division

they acquire round shape. Then they undergo mitosis to duplicate themselves. After mitosis, we have two identical cells, identical to the parental cell. So, cell division increases the number of cellular precursors in the neural tube. However, while some cells continue to proliferate, others start to differentiate after mitosis. The two cells generated after mitosis are different: one is the cell linked to the neuronal tube, while the other can become a neuronal cell. But how do the neuronal cells know what to become? The dorsal part of the neuronal tube is mostly influenced by molecules released by the ectoderm, while the ventral part of the neuronal tube is mostly influenced by signaling molecules released by the notochord. These molecules play a crucial role in shaping our brain. - High levels of BMP and Wnt signals at the neural crest influence the development of sensory cells. - High levels of Sonic hedgehog signals at the floorplate influence the development of motor neurons. - This concentration of signaling molecules determines the fate of the cells in the neural tube.gradient of BMP, Wnt, and Shh and its effects on development is called dorsoventral patterning. (depends on the concentration gradient)

Dorsoventral Patterning

Below the neural tube there is the notochord that is the source of signaling molecules, there is a molecule called sonicedok (shh) that is very abundant at the central part of the neural tube and at the level of notochord.

While we move far from the source of signaling molecules the concentration gradient decreases, that means cells that are closer to the source will be more influenced by the power of the signaling molecules. So neural precursors sitting along the neural tube will be subjected to a different influence by signaling molecules, this mechanism is named dorsoventral patterning. Neural precursors sitting in different subregions are differently influenced by signaling molecules and give rise to different neuronal targets. The amount of chemicals that a cell is exposed to influences how it

develops.Neural Induction All the molecules called like BMP-4 etc bound to receptors placed into the plasmamembrane of ectodermal cells, by activated these receptors they triggered a signaling cascade leads to the transcriptional activation of targeted genes. Also noggin, cordin and follistatin molecules named are provided by notochord. they inhibit the activity of bond morfogenetic proteins. Thanks to this mechanism part of the cells escape the fate of becaming skin cells and induced to become neural precursor cells. The ectodermal BMP-4 inhibits the formation of neural tube. The notocord, which originates from mesoderm produces noggin, cordin and follistatin. These molecules counteract the BMP-4 activity favoring the neural tube formation. How this precursors cells they originate different neuronal cells and different glia cells type? Neuro epitilial cells, they have shape similar to a column, they are connected to the paraventricular cavity at one site and on the other site to pyal surface. At

In the first stage of neurodevelopment, there is cell proliferation (mitosis), followed by the generation of post-mitotic cells that start to generate neurons. Once these cells become post-mitotic, they exit the cell cycle and leave the ventricular zone, migrating to the opposite part of the ventricular zone of the neuronal tube.

During neuronal migration, radial glial cells, which were previously neuroepithelial cells, play an important role. After the formation of the neural tube, neuroepithelial cells transform into radial glial cells. These cells provide a network where neurons can establish contact with molecules.

Neural precursor cells give rise to both neurons and glial cells, thanks to astrocytes. When a cell divides, there is a split of the nucleus content (genetic information and cytoplasm), which contains proteins. Many of these proteins act as transcription factors. In response to specific stimuli, they translocate into the nucleus and bind to the promoter region of genes, activating transcription.

So when the cells split there is also a separation of molecules. This introduce the concept of Symmetric cell division and asymmetric cell division. When a cell division is symmetric the split part are identical in term of nucleus content (genetic information and cytoplasm composition), a cell division is asymmetric when the 2 cells that are generated they are provided with the exactly the same genetic information but they are different with cytoplasm content. This is guided by signaling molecules, they activated different transcriptional pathway so they acquired in their cytoplasm specific protein. So the transcription program of this cells become different, so they acquired different proteins. A morphogen is a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positions of the various specialized cell types within a tissue. More specifically, a is a signaling molecule that acts directly on cells to produce specific cellular responses depending on its local concentration. Typically, morphogens are produced by source cells and diffuse through surrounding tissues in an embryo during early development, such that concentration gradients are set up. These gradients drive the process of differentiation of unspecialized stem cells into different cell types, ultimately forming all the tissues and organs of the body.

How Does the Brain Form?

The primordial brain is split into various regions that give rise to various components of the adult brain. The rostral ("front") part of the neural tube undergoes several folds and changes to shape it into:

• Prosencephalon (Forebrain)
• Mesencephalon (Midbrain)
• Rhombencephalon (Hindbrain)

The Prosencephalon is divided into:

1. Telencephalon that generates:
• Cerebral Cortex
• Hippocampus
• Basal Ganglia
2. Diencephalon that generates:
• Thalamus
• Hypothalamus
• Optic

CupsMesencephalon- Superior Colliculus - Inferior Colliculus - Midbrain TegmentumRhombencephalon- 1)Metencephalon gives rise to ° Cerebellum ° Pons2)Myencelencephalon gives rise to ° MedullaAnd How Do These Regions Know What to Become?- concentration gradient based on signaling molecules, it’s a gradient of faibroglasgrow factor family (FGF) and Retinoic acid, which affect the expression of homeobox(Hox) transcription factors. This is known as rostrocaudal patterning.Every vertebrate animal has a cell body has a division of axis based of bodyorganization, the fruit fly embryo there are part that anticipated which part becomethe posterior part and the anterior part of the body. This is connected to the homeoticgenes.Homeotic gene is a gene that controls the pattern of body formation during earlyembryonic development of organisms. Homeotic genes encode proteins calledtranscription factors that direct cells to form various parts of the body. A homeoticprotein can

activate one gene but repress another, producing effects that are complementary and necessary for the ordered development of an organism. With reference of neural tube, the first subregion of neural tube expresses homeotic genes that have a specific identity that activate a transcription program. The ordered expression of the homeotic genes along various regions of neural tube, and more generally along various regions that form a developing organism, this allows the proper development so the differentiation of the anterior part and other parts.

Homeotic genes were first discovered in Drosophila (fruit fly). Homologous to those genes were later found in a wide range of organisms, including fungi, plants, and vertebrates. In vertebrates, these genes are commonly referred to as HOX genes. Humans possess some 39 HOX genes, which are divided into four different clusters, A, B, C, and D, which are located on different chromosomes.

What If Things Go Wrong? - Changing the expression of even just one

homeoboxtranscription factor can have a huge effect!

Migration and Aggregation + Radial glia

Undifferentiated cells start migration, they only have soma and an immature axon, with no dendrites.

Differentiation begins with migration: they develop neurotransmitters and action potentials. Cells migrate away from the ventricular zone along a temporary network of radial glial cells, which are present in only the developing neural tube, which then act as guide wires and present in the developing tube only. Radial glial cells represent the precursors generating neurons and glial cells in a second moment. After migration cells align themselves with other cells and form structures: aggregation.

Development of cerebral cortex

The cortex is organized in 6 layers, each has specific neuronal types with given morphological features. The cortex reminds the neural tube wall: there is the cavity that is the ventricular zone where there are neurogenic niches, only a f