NEUR2202 lecture 1 - Natalina Salmaso PDF

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Natalina Salmaso...

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NEUR2202: Lecture 1

Animals ● Protozoan: single cell animal. Reproduces by splitting in 2 ● Evolution favoured cells clumping together by increasing chances of survival ● Metazoan: multicell animal (human) ● Cnidarians (ex: jellyfish, anemones…) didn’t have brains but instead specialized cells making up a nerve net (system of interconnected neurs) ○ There are very few cells, so they only have basic processes ● Vertebrates: early in dev, they all look alike ○ As they mature, they become more and more complex, stopping at various points ○ Forebrain, midbrain, and hindbrain are visible in human embryo at about 28 days Dev or the human NS ● Prenatal stages ○ Zygote: fertilization to 2 weeks ○ Embryo: 2-8 wks ○ Fetus: 9 wks to birth ● Neural plate (3 wks after conception) ○ Thickened region of the ectodermal layer that gives rise to the neural tub ○ Will become the NS ● Neural tube ○ Structure in the early stage of brain dev from which the brain and SC dev ● Major events ○ Day 49: embryo begins to resemble a mini person ○ Day 60: sexual dif and dev and certain brain regions ○ Day 100: brain looks distinctly human ○ 7 months: gyri and sulci on the brain begin to form (larger surface) ○ 9 months: brain looks like an adult brain Historical perspective on dev biology ● Aristotle suggested epigenesis ○ Process by which the body gradually changes shape, acquiring new structures and growing more and more complex over time ● The dev of microscopes allowed more in depth analysis of dev and anatomical structure ● Challenged epigenesis with preformation ○ Preformation: theory that a mini version of the organism is inside the sperm and will dev into the embryo once implanted, dev consists of a simple enlargement of a body plan that was always In place ○ Preformation was discredited as a theory and epigenesis is correct Ontogeny ● The process of individual dev (neural ontogeny in this course) ● Early embryos are clumps of cells, and as ontogeny proceeds, the more and more complex

tissue will appear Nucleus ● Site of gene transcription ● Chromosome: double helix structure that holds an organism's entire DNA sequence (contain genes) ○ Nucleotide bases: adenine, thymine, guanine and cytosine ○ Somatic cells have 23 pairs ● Gene ○ Segment of DNA that encodes the synthesis of particular proteins ○ Sequences of nucleotides determine which amino acids are to be joined to form the particular protein Use it, lose it ● Discarded theory that cells lose the genes that are not used ○ We now know gene expression is regulated ● Clones were used to disprove this theory ○ The nucleus of an albino frogs skin cell was implanted into the enucleated egg from a pigmented frog. This produces a whole albino frog with the genetic characteristic of the skin cell ○ If the skin cell had lost the genes it was not using, an entire frog would not have been dev Regulatory regions of genes ● Transcription factor: a protein that binds to DNA to regulate gene transcription ○ Can activate or repress by binding to a certain regulatory portion of the gene ○ Introns: stretches of DNA that do not contribute to the final mRNA molecule, but may play a role in regulating transcription ○ Dif transcription factors are present in dif parts of the body (in various concentrations) Caenorhabditis elegans ● Nematode worm often used in research because cells can easily be identified and tracked in the living worm ● Microscopic, transparent, most are hermaphrodites ● Mitotic lineage revels cell fata ○ Their cell specification is determined really early on in dev, and after that the cells can only go down one path Mosaic cell specification determines cell fate in worms ● ●

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Get transcription factors from mother Initial cell (egg) has all the cell components, like cytoplasm, that contains the transcription factors ○ Sperm pretty much just contributes DNA When the cell divides, the various transcription factors are unevenly distributed to the 2

daughter cells, beginning cell specification Self regulation in embryos ● Any of the blastomeres at the 4 cell stage could make a complete organism ○ If cells were on a specific path, taking one of them shouldn't make a complete animal ○ Any of these nuclei, when put back into the original environment that hasn't started to dev, will become an entire animal ● Removing a batch of cells does not seem to disrupt the body plan ○ No body structure is missing ● Self regulation: the process by which embryos manage to compensate for mission or damaged cells can still produce and entire organism ○ Form of plasticity ● Totipotent: capable of becoming any cell type, or complete embryo ● Pluripotent: capable of becoming several cell types ● Multipotent: capable of becoming more than one cell type, but are much more limited than pluripotent cells Conditional specification of cell fate ● Induction: process by which one group of cells directs the differentiation of other nearby cells ○ Ex: when the optic cup is formed, the epidermis next to it becomes the cornea and the len ● Find it, move it, lose it ○ To find out how something devs, look at what factors are present in the environment. Then test which is the important factor by moving it. If the tissue of interest does not dev in the new area (with the factor being studied) then you know that factor is not inducing the dev) ○ Implanted optic cup in a dif area induces the ectoderm to form a lens Embryonic dev ● Earliest embryos form a hollow blastula ● Amphibian embryonic dev ○ The 3 germ layers, in the gastrula, each make a dif contribution to the body ● Mammalian embryonic dev ○ Cells that form the neural tube can be thought of as the nursery for the rest of the CNS ○ The open region in the center of the tube remains open and matures into the brains ventricles and the SC ● Super-inducer ("the organizer"): the dorsal lip region of the blastopore. Starting point of embryonic specification ○ Noggin: transcription factor ■ Noggin mRNA in the dorsal lip of the blastopore ■ If you knock-out noggin, you get a smaller head but not the absence of one, suggesting there are more factors contributing to the dev but noggin in an important one

The dorsal lip of the blastopore becomes the mesoderm, which in turn releases noggin to block the TGF-beta rec (antagonist). This does not allow BMP (secreted by ectodermal cells) to bind and so those cells don’t become skin cells, instead becoming neural cells ○ Dif concentrations of organizer-like signals allows certain areas to follow the path of neural differentiation, while other areas experience a lot of BMP signalling, becoming skin cells Accumulation of endodermal beta-catenin induces mesoderm to become the organizer (dorsal lip) ○ Beta-catenin is not one of the transcription factors from the mother ○ Overexpressed beta-catenin leads to too much neural dev and death of transgenic mice ○ Maternal-derived gradients of transcription factors are likely involved in inducing beta- catenin release from the endoderm ○

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Cell-cell interaction , ● Juxtacrine: signalling that requires physical interaction between cells ● AS_C: pro-neural gene In insects found in every cell (unlike noggin) ○ Delta as a ligand th at is expressed on the cell surface of the signalling cell. Delta binds to a receiver, called notch, forming the delta-notch complex. This interaction leads to the cleavage of the intracellular domain of notch by proteases. Notch fragment goes to the nucleus and binds to the enhancer of split, inhibiting the transcription of AS-C, and repressing delta production ○ This entire process is called lateral inhibition (juxtacrine)...