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Axis Formation 2
Physiology and Pharmacology
| Question | Answer |
|---|---|
| How do cells move | By changing shape Often involves a epithelial - mesenchymal transition Mesoderm moves in all directions |
| What does ectoderm form | Epidermis Neural tissue and neural crest |
| How does neurulation occur | Dorsal mesoderm induces cells to change shape and fold to induce the neural plate (week 3) These form neural folds by cell invagination The cells converge and form a complete circle Epidermal layer closes off on top to form epidermis |
| Role of somites in neurulation | Somites form from rostral region They move down towards the caudal side to form a neural tube They leave open ends that seal at different times - Anterior closes at 25 days whilst posterior closes at 27 days |
| Anencephaly | Failure to close anterior neuropore Often survive to late fetal life/term but die within hours /days |
| Neural crest cell migration | Cells undergo an epithelial to mesenchymal transition and migrate into underlying mesoderm E.g. neural crest cells form dorsal root ganglion, sympathetic ganglion and enteric ganglia Can also from structures around the body |
| Role of neural crest cells in the heart | Cells from the rostral neural crest form the aorticopulmonary septum These prevent mixing of blood in the aorta and pulmonary artery |
| Melanocyte development | Derivatives of the neural crest Defects in neural crest development and migration produce pigmentation defects e.g. dominant piebald trait from mutation of receptor tyrosine kinase kit Can lead to patches of unpigmented skin on ventral side |
| Mesoderm | Forms everything that endoderm and ectoderm don't Prechordal (head and cardiogenic) Axial (notochord) Paraxial (somites) Intermediate (urogenital system) Lateral plate (limbs) |
| Notochord | Initially a tube-becomes a solid rod of cells Forms nucleus pulposus- intervertebral disks Forms primitive axis around axial skeleton is formed Patterns neural tube along D/V axis - Shh Located at dorsal axis - extends as primitive node regresses |
| Segment polarity genes | Identified in fruit flies Saturation mutagenesis screen - generated 1000s of mutations - see which ones have an effect Many mutations had segment polarity defects - defects in all segments Often involved in hedgehog/WNT signalling - all had same effect |
| Hedgehog signalling cascade | Used repetitively in humans to control patterning - highly conserved Binds to a protein that usually represses Smo Allows TF into cell which alters gene regulation |
| Neural induction | Shh from the notochord and most ventral neural tube cells forms a conc gradient across neural tube Induces different ventral fates whilst BMPs regulate dorsal fates (produced by ectoderm) High Shh- motor neurons Hight BMP - sensory neurons |
| Conserved signalling | Identified WNT and hedgehog signalling cascades and highlighted several novel components in TGF-beta, RTK etc Small numbers of signalling cascades control most of development Somites receive lots of signals from different tissues - form different cells |
| Paraxial mesoderm | Somites form in a cephalocaudal direction Occipital somites at day 20 Progresses at 3 pairs a day At end of 4th week - 12 thoracic, 5 lumbar, 5 sacral and 8-12 coccygeal Produce many mesoderm derived structures along R/C axis |
| Somites | Form Sclerotome - vertebrae and vertebral discs Form Dermomyotome - dermatome forms dermis myotome forms dorsal and ventral muscles Notochord, neural tube, ectoderm and lateral plate - inductive cues |
| Sclerotome formation | Beginning of 4th week - ventral and medial cells of somite move to surround notochord and neural tube - sclerotome - Vertebral body, annulus fibrosus and vertebral arch Costal processes - ribs Failure of migration on one side - lateral scoliosis |
| Formation of spinal nerves and vertebral body | Spinal nerves - segmental development, move through vertebrae to cut them in half Sclerotomes split and recombine to form vertebral rudiments Ones above nerve form bottom of upper vertebrae and vice versa |
| Types of Spina Bifida | Spina bifida occulta - lower lumbar/sacral - no other symptoms as arch can fuse later Spinal bifida cystica - genetic, neural tube exposed Meningocele - only lining exposes Meningomyelocele - both lining and neural tube exposed |
| Effects of Spina bifida | Can affect pelvic organs and legs Blocks CSF flow - hydrocephaly (excess fluid in head) |
| Cause of spina bifida | Possible genetic Valproic acid in the 4th week |
| Epaxial/Hypaxial myotome formation | Dorsolateral cells in the somite migrate ventrally - limb and body wall musculature - Hypaxial myotome Dorsomedial cells then proliferate to form epaxial myotome or dorsal epimere, whilst rest of somite - dermatome - dermis - Epaxial myotome |
| Role of cell-cell signalling | Developmental signalling molecules from a limited repertoire of gene families are recruited on multiple occasions to pattern developing structures For somite specification, multiple signalling centres are used to specify position |
| What does lateral plate mesoderm form | Parietal - lateral and ventral body wall e.g. dermis and limb buds' Visceral wall of gut surrounding cells of the endoderm |
| Role of Hox genes in specification | Identified in drosophila House Hoxc8 controls which vertebrae form If hox gene not expressed defects occur e.g. excess vertebrae Somites are mis specified |
| Role of endoderm in gut tube lining | Neural tube forms at top of embryo Gut tube forms at the bottom and pinches the endoderm cells off to form a hollow tube Also contains cells that will form the heart - must migrate down |
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