| Neurulation |
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Transverse sections that show the progression of the neural plate to the neural groove from bottom to top
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| Anatomical terminology
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Neurulation refers to the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube.[1] The embryo at this stage is termed the neurula.
The process begins when the notochord induces the formation of the central nervous system (CNS) by signaling the ectoderm germ layer above it to form the thick and flat neural plate. The neural plate folds in upon itself to form the neural tube, which will later differentiate into the spinal cord and the brain, eventually forming the central nervous system.[2]
Different portions of the neural tube form by two different processes, called primary and secondary neurulation, in different species.[citation needed]
- In primary neurulation, the neural plate creases inward until the edges come in contact and fuse.
- In secondary neurulation, the tube forms by hollowing out of the interior of a solid precursor.
Contents
- 1 Primary neurulation
- 1.1 Induction
- 1.2 Shape change
- 1.3 Folding
- 1.4 Patterning
- 1.5 Complexities of the model
- 2 Secondary neurulation
- 3 Early brain development
- 4 Non-neural ectoderm tissue
- 5 Neural crest cells
- 6 Neural tube defects
- 7 See also
- 8 References
- 9 Further reading
- 10 External links
Primary neurulation
Cross section of a vertebrate embryo in the neurula stage
Induction
Primary neurulation occurs in response to soluble growth factors secreted by the notochord. Ectodermal cells are induced to form neuroectoderm from a variety of signals. Ectoderm sends and receives signals of bone morphogenetic protein 4 (BMP4) and cells which receive BMP4 signal develop into epidermis. The inhibitory signals chordin, noggin and follistatin are needed to form neural plate. These inhibitory signals are created and emitted by the Spemann's organiser. Cells which do not receive BMP4 signaling due to the effects of the inhibitory signals will develop into the anterior neuroectoderm cells of the neural plate. Cells which receive fibroblast growth factor (FGF) in addition to the inhibitory signals form posterior neural plate cells.[citation needed]
Shape change
The cells of the neural plate are signaled to become high-columnar and can be identified through microscopy as different from the surrounding epiblastic ectoderm. The cells move laterally and away from the central axis and change into a truncated pyramid shape. This pyramid shape is achieved through tubulin and actin in the apical portion of the cell which constricts as they move. The variation in cell shapes is partially determined by the location of the nucleus within the cell, causing bulging in areas of the cells forcing the height and shape of the cell to change. This process is known as apical constriction[citation needed]
Folding
The process of the flat neural plate folding into the cylindrical neural tube is termed primary neurulation. As a result of the cellular shape changes, the neural plate forms the medial hinge point (MHP) . The expanding epidermis puts pressure on the MHP and causes the neural plate to fold resulting in neural folds and the creation of the neural groove. The neural folds form dorsolateral hinge points (DLHP) and pressure on this hinge causes the neural folds to meet and fuse at the midline. The fusion requires the regulation of cell adhesion molecules. The neural plate switches from E-cadherin expression to N-cadherin and N-CAM expression to recognize each other as the same tissue and close the tube. This change in expression stops the binding of the neural tube to the epidermis. Neural plate folding is a complicated step.[citation needed]
The notochord plays an integral role in the development of the neural tube. Prior to neurulation, during the migration of epiblastic endoderm cells towards the hypoblastic endoderm, the notochordal process opens into an arch termed the notochordal plate and attaches overlying neuroepithelium of the neural plate. The notochordal plate then serves as an anchor for the neural plate and pushes the two edges of the plate upwards while keeping the middle section anchored. Some of the notochodral cells become incorporated into the center section neural plate to later form the floor plate of the neural tube. The notochord plate separates and forms the solid notochord.[citation needed]
The folding of the neural tube to form an actual tube does not occur all at once. Instead, it begins approximately at the level of the fourth somite at Carnegie stage 9 (around Embryonic day 20 in humans). The lateral edges of the neural plate touch in the midline and join together. This continues both cranially (toward the head) and caudally (toward the tail). The openings that are formed at the cranial and caudal regions are termed the cranial and caudal neuropores. In human embryos, the cranial neuropore closes approximately on day 24 and the caudal neuropore on day 28.[3] Failure of the cranial (anterior) and caudal (posterior) neuropore closure results in conditions called anencephaly and spina bifida, respectively. Additionally, failure of the neural tube to close throughout the length of the body results in a condition called rachischisis.[4]
Patterning
Transverse section of the neural tube showing the floor plate and roof plate
After sonic hedgehog (SHH) signalling from the notochord induces its formation, the floor plate of the incipient neural tube also secretes SHH. After closure, the neural tube forms a basal or floor plate and a roof or alar plate in response to the combined effects of SHH and factors including BMP4 secreted by the roof plate. The basal plate forms most of the ventral portion of the nervous system, including the motor portion of the spinal cord and brain stem; the alar plate forms the dorsal portions, devoted mostly to sensory processing.[5]
The dorsal epidermis expresses BMP4 and BMP7. The roof plate of the neural tube responds to those signals to express more BMP4 and other transforming growth factor beta (TGF-β) signals to form a dorsal/ventral gradient among the neural tube. The notochord expresses SHH. The floor plate responds to SHH by producing its own SHH and forming a gradient. These gradients allows for the differential expression of transcription factors.[6]
Complexities of the model
In actuality, the folding of the neural tube is still not entirely understood and is still being studied. The simplistic model of the closure occurring in one step cranially and caudally does not explain the high frequency of neural tube defects (see below). Proposed theories include that closure of the neural tube occurs in regions, rather than entirely linearly.[citation needed]
Secondary neurulation
In secondary neurulation, the neural ectoderm and some cells from the endoderm form the medullary cord. The medullary cord condenses, separates and then forms cavities.[citation needed] These cavities then merge to form a single tube. Secondary neurulation occurs in the posterior section of most animals but it is better expressed in birds. Tubes from both primary and secondary neurulation eventually connect.[7]
Early brain development
The anterior portion of the neural tube forms the three main parts of the brain: the forebrain (prosencephalon), midbrain (mesencephalon), and the hindbrain (rhombencephalon).[8] These structures initially appear just after neural tube closure as bulges called brain vesicles in a pattern specified by anterior-posterior patterning genes, including Hox genes, other transcription factors such as Emx, Otx, and Pax genes, and secreted signaling factors such as fibroblast growth factors (FGFs) and Wnts.[9] These brain vesicles further divide into subregions. The prosencephalon gives rise to the telencephalon and diencephalon, and the rhombencephalon generates the metencephalon and myelencephalon. The hindbrain, which is the evolutionarily most ancient part of the chordate brain, also divides into different segments called rhombomeres. The rhombomeres generate many of the most essential neural circuits needed for life, including those that control respiration and heart rate, and produce most of the cranial nerves.[10] Neural crest cells form ganglia above each rhombomere. The early neural tube is primarily composed of the germinal neuroepithelium, later called the ventricular zone, which contains primary neural stem cells called radial glial cells and serves as the main source of neurons produced during brain development through the process of neurogenesis.[11][12]
Non-neural ectoderm tissue
Paraxial mesoderm surrounding the notochord at the sides will develop into the somites (future muscles, bones, and contributes to the formation of limbs of the vertebrate ).[citation needed]
Neural crest cells
Main article: Neural crest
Masses of tissue called the neural crest that are located at the very edges of the lateral plates of the folding neural tube separate from the neural tube and migrate to become a variety of different but important cells.[citation needed]
Neural crest cells will migrate through the embryo and will give rise to several cell populations, including pigment cells and the cells of the peripheral nervous system.[citation needed]
Neural tube defects
Closure of the neural tube occurs in the middle, and then moves superiorly and inferiorly. Failure to close the superior neural tube results in anencephaly, a condition characterised by forebrain and skull degeneration, which is always fatal. Failure to close the inferior tube is known as spina bifida, which in its most severe form is characterised by failure to form the neural plate (bifida is derived from Latin, to mean 'cleft in two parts'). Less severe forms are characterised by defects in the meninges and vertebrae which overlie the posterior spinal cord.[13]
Spina bifida can lead to paralysis beneath the affected region of the spinal cord. Sufferers may require crutches or wheelchairs to move about, and may also suffer from lack of bladder and bowel control.[citation needed]
Neural tube defects are among the most common and disabling birth defects, occurring in roughly 1 in every 500 live births.[14]
See also
- Neural fold
- Neural plate
- Neural crest
References
- ^ Larsen WJ. Human Embryology. Third ed. 2001.P 86. ISBN 0-443-06583-7
- ^ "Chapter 14. Gastrulation and Neurulation". biology.kenyon.edu. Retrieved 2 February 2016.
- ^ Youman's Neurological Surgery, H Richard Winn, 6th ed. Volume 1, p 81, 2011 Elsevier Saunders, Philadelphia, PA
- ^ Gilbert, SF (2000). "12: Formation of the Neural Tube". Developmental Biology (6 ed.). Sunderland, MA: Sinauer Associates. ISBN 978-0-87893-243-6. Retrieved 30 November 2011.
- ^ Gilbert, SF (2013). "10: Emergence of the Ectoderm". Developmental Biology (10 ed.). Sunderland, MA: Sinauer Associates. ISBN 978-0-87893-978-7. Retrieved 22 March 2015.
- ^ Gilbert, SF (2013). "10: Emergence of the Ectoderm". Developmental Biology (10 ed.). Sunderland, MA: Sinauer Associates. ISBN 978-0-87893-978-7. Retrieved 22 March 2015.
- ^ Shimokita, E; Takahashi, Y (April 2011). "Secondary neurulation: Fate-mapping and gene manipulation of the neural tube in tail bud.". Development, growth & differentiation. 53 (3): 401–10. doi:10.1111/j.1440-169X.2011.01260.x. PMID 21492152.
- ^ Gilbert, Scott F.; College, Swarthmore; Helsinki, the University of (2014). Developmental biology (Tenth ed.). Sunderland, Mass.: Sinauer. ISBN 978-0878939787.
- ^ Principles of neural science (5. ed.). Appleton and Lange: McGraw Hill. 2006. ISBN 978-0071390118.
- ^ Gilbert, Scott F.; College, Swarthmore; Helsinki, the University of (2014). Developmental biology (Tenth ed.). Sunderland, Mass.: Sinauer. ISBN 978-0878939787.
- ^ Rakic, P (October 2009). "Evolution of the neocortex: a perspective from developmental biology.". Nature Reviews. Neuroscience. 10 (10): 724–35. doi:10.1038/nrn2719. PMC 2913577 . PMID 19763105.
- ^ Dehay, C; Kennedy, H (June 2007). "Cell-cycle control and cortical development.". Nature Reviews. Neuroscience. 8 (6): 438–50. doi:10.1038/nrn2097. PMID 17514197.
- ^ Bear, Mark (2009). Neuroscience - Exploring the Brain. LWW. pp. 182–183.
- ^ Daley, Darrel. Formation of the Nervous System. Last accessed on Oct 29, 2007.
Further reading
- Almeida, Karla L.; et al. (2010). "Neural Induction". In Henning, Ulrich. Perspectives of Stem Cells: From Tools for Studying Mechanisms of Neuronal Differentiation Towards Therapy. Springer. ISBN 978-90-481-3374-1.
- Basch, Martín L. & Bonner-Fraser, Marianne (2006). "Neural Crest Inducing Signals". In Saint-Jennet, Jean-Pierre. Neural crest induction and differentiation. Springer. ISBN 978-0-387-35136-0.
- Harland, Richard M. (1997). "Neural induction in Xenopus". In Cowan, W. Maxwell. Molecular and cellular approaches to neural development. Oxford University Press. ISBN 978-0-19-511166-8.
- Ladher, Raj & Schoenwolf, Gary C. (2004). "Making a neural tube". In Jacobson, Marcus & Rao, Mahendra S. Developmental neurobiology. Springer. ISBN 978-0-306-48330-1.
- Tian, Jing & Sampath, Karuna (2004). "Formation and Functions of the Floor Plate". In Gong, Zhiyuan & Korzh, Vladimir. Fish development and genetics: the zebrafish and medaka models. World Scientific. pp. 123; 139–140. ISBN 978-981-238-821-6.
- Zhang, Su-Chun (2005). "Neural specification from human embryonic stem cells". In Odorico, John S. et al. Human embryonic stem cells. Garland Science. ISBN 978-1-85996-278-7.
External links
- Overview at uvm.edu
- Neurulation Animation
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Human embryogenesis in the first three weeks
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| Week 1 |
- Fertilization
- Oocyte activation
- Zygote
- Cleavage
- Blastomere
- Morula
- Blastocoele
- Blastocyst
- Blastula
- Inner cell mass
- Trophoblast
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Week 2
(Bilaminar) |
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Week 3
(Trilaminar) |
| Germ layers |
- Archenteron/Primitive streak
- Primitive pit
- Primitive knot/Blastopore
- Primitive groove
- Gastrula
- Regional specification
- Embryonic disc
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| Ectoderm |
- Surface ectoderm
- Neuroectoderm
- Somatopleuric mesenchyme
- Neurulation
- Neural crest
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| Endoderm |
- Splanchnopleuric mesenchyme
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| Mesoderm |
- Axial mesoderm
- Paraxial
- Intermediate
- Lateral plate
- Intraembryonic coelom
- Splanchnopleuric mesenchyme
- Somatopleuric mesenchyme
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Development of the nervous system
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| Neurogenesis |
| General |
- Neural development
- Neurulation
- Neurula
- Notochord
- Neuroectoderm
- Neural plate
- Neural fold
- Neural groove
- Neuropoiesis
- Adult neurogenesis
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| Neural crest |
- Cranial neural crest
- Cardiac neural crest complex
- Truncal neural crest
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| Neural tube |
- Rostral neuropore
- Neuromere / Rhombomere
- Cephalic flexure
- Pontine flexure
- Alar plate
- Basal plate
- Glioblast
- Neuroblast
- Germinal matrix
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| Eye |
- Neural tube
- Optic vesicle
- Optic stalk
- Optic cup
- Surface ectoderm
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| Ear |
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