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| = Neural Crest Development=
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| == Introduction ==
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| The neural crest are bilaterally paired strips of cells arising in the ectoderm at the margins of the neural tube. These cells migrate to many different locations and differentiate into many cell types within the embryo. This means that many different systems (neural, skin, teeth, head, face, heart, endocrine, gastrointestinal tract) will also have a contribution fron the neural crest cells.
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| In the body region, neural crest cells also contribute the peripheral nervous system (both neurons and glia) consisting of sensory ganglia (dorsal root ganglia), sympathetic and parasympathetic ganglia and neural plexuses within specific tissues/organs.
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| In the head region, neural crest cells migrate into the pharyngeal arches (as shown in movie below) forming '''ectomesenchyme''' contributing tissues which in the body region are typically derived from mesoderm (cartilage, bone, and connective tissue).
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| General neural development is also covered in Neural Notes.
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| :'''Lectopia Audio''' Lecture Date: 01-09-2009 Lecture Time: 12:00 Venue: BioMed E Speaker: Mark Hill [http://lectopia.elearning.unsw.edu.au/ilectures/ilectures.lasso?ut=153&id=48840 Neural Crest]
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| ==Lecture Objectives==
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| * Understand the structures derived from ectoderm.
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| * Understand the formation of neural folds.
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| * Identify the initial location of neural crest cells in the trilaminar embryo.
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| * Identify pathways of neural crest migration throughout the embryo.
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| * To know the major tissues to which neural crest cells contribute.
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| * To know how abnormalities in development that result from abnormal neural crest cell migration.
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| * Understand how neural crest cells contribute to the pharyngeal arches and the head structures they form.
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| == Textbook References ==
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| * '''The Developing Human: Clinically Oriented Embryology''' (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 4 p61-63 - p71,75, 385, 392 p393-94 (figure showing cell types); Chapter 10 The Pharyngeal Apparatus pp201 - 240,
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| * '''Larsen’s Human Embryology''' by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 4 p74-82 - Chapter 5, experimental methods; Chapter 12 Development of the Head, the Neck, the Eyes, and the Ears pp349 - 418
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| ==Early Development and Neural Derivatives==
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|
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| * bilaminar embryo- hyoblast
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| * trilaminar embryo - ectoderm layer
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| ** neural plate - neural groove - neural tube and neural crest
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| * cranial expansion of neural tube - central nervous system
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| * caudal remainder of neural tube - spinal cord
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| Neural Crest
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| * dorsal root ganglia
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| * parasympathetic / sympathetic ganglia.
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| * ectodermal placodes- components of the special senses
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| * Sensory placodes - otic placode (otocyst), nasal placode, lens placode
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| ==Neural Crest Origin==
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| [[File:Neuralplate cartoon.png|left]]
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| * lateral region of neural plate
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| * dorsal neural fold->tube
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| Two main embryo regions
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| * Head (CNS) - differentiate slightly earlier, mesencephalic region of neural folds
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| * Body (spinal cord) - lateral edges of fused neural tube
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| == Neural Crest Generation ==
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|
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| * cranial region - Begins when still neural fold
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| * spinal cord - from day 22 until day 26
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| ** after closure of caudal neuropore
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| ** rostro-caudal gradient of differentiation
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| Studies using the chicken model demonstrated that they are not a segregated population. Interactions between the neural plate and epidermis can generate neural crest cells, since juxtaposition of these tissues at early stages results in the formation of neural crest cells at the interface.
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| At cranial levels, neuroepithelial cells can regulate to generate neural crest cells when the endogenous neural folds are removed, probably via interaction of the remaining neural tube with the epidermis.
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| Progenitor cells in the neural folds are multipotent, having the ability to form multiple ectodermal derivatives, including epidermal, neural crest, and neural tube cells the neural crest is an induced population that arises by interactions between the neural plate and the epidermis.
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| The competence of the neural plate to respond to inductive interactions changes as a function of embryonic age.
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| (Text from: Bronner-Fraser M PNAS 1996 Sep 3;93(18):9352-7)
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| == Neural Crest Derivatives ==
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| Neural crest progenitor cells migrate throughout the embryo and give rise to many different adult cells.
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| This Includes: ganglia cranial, dorsal root, sympathetic trunk, celiac, renal, plexus in GIT, glia, schwann cells, melanocytes (skin), and adrenal medulla (chromaffin cells).
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| In the head region neural crest also gives rise to a number of connective tissue structures.
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| ===Neural Crest - Head===
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| (see also [[2009_Lecture_11|Head Development Notes]])
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| Mesencephalon and caudal Proencephalon
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| * parasympathetic ganglia CN III
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| * connective tissue around eye and nerve
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| * head mesenchyme
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| * pia and arachnoid mater
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| * dura from mesoderm
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| Mesencephalon and Rhombencephalon
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| * pharayngeal arches
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| * look at practical notes on neck and head.
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| * cartilage rudiments (nose, face, middle ear)
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| * face
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| * dermis, smooth muscle and fat
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| * odontoblasts of developing teeth
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| Rhombencephalon
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| * C cells of thyroid
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| * cranial nerve ganglia
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| * neurons and glia
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| * parasympathetic of VII, IX, X
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| * sensory ganglia of V, VII, VIII, IX, X
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| ===Neural Crest- Spinal Cord===
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| * peripheral nervous system
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| * dorsal root ganglia (sensory N)
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| * parasympathetic ganglia
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| * sympathetic ganglia
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| * motoneurons in both ganglia
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| * all associated glia
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| == Neural Crest Migration ==
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| [[File:Human neural crest cell migration-in vitro.jpg|thumb|Human neural crest cell migration (in vitro)<ref><pubmed>18689800</pubmed>| [http://hmg.oxfordjournals.org/cgi/content/full/17/21/3411 Hum Mol Genet.]</ref>]]
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| ===Head===
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| [[File:Neural-crest-migration7.jpg|240px]][[File:Neural-crest-migration6.jpg|240px]]
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| [[File:Neural_Crest_Migration7.mov]] | [[File:Neural_Crest_Migration6.mov]] | [[:Category:Movies]]
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| ===Trunk===
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| [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.3118 Figure 13.2. Neural crest cell migration in the trunk of the chick embryo]
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| * Neural crest at the level of the body have two general migration pathways, defined by the position of the somite
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| ** medial pathway - between the neural tube and the somite
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| ** lateral pathway - between the somite and the body wall
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| [[File:Trunk neural crest migration.jpg|thumb|Trunk neural crest migration]]
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| * A recent study of guidance of neural crest cells (NCC) in mice show migrate 3 specific pathways.
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| ** SEMA3A and its receptor neuropilin 1 (NRP1) - act as repulsive guidance cues
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| ** migration pathway did not affect specification - differs from the concept of migration pathway specifying the neural crest cell differentiation pathway
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| Neural crest at the level of the head have a different migration pathway. [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.3134 Figure 13.7. Cranial neural crest cell migration in the mammalian head]
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| ===Sympathetic Ganglia and Adrenal Medulla===
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| [[File:Adrenal_medulla.jpg]]
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| [[Media:Adrenal_medulla.mov]]
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| ===Enteric nervous system===
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| [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A63004&rendertype=figure&id=A63009 Figure 1. Diagram of an E10 embryo showing the origins of neural crest cells that colonize the developing gastrointestinal tract]
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| ===Historic Migration Experiments===
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| Key early experiments in understanding the pattern of neural crest migration were carried out by LeDouarin in the 1980's (see Development of the peripheral Nervous system from the neural crest, Ann Rev Cell Biol 4 p375)
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| [http://www.sdbonline.org/archive/dbcinema/ledouarin/ledouarin.html Quail-Chick Chimeras] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.63 Figure 1.11. Neural crest cell migration Chimera experiment]
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| These transplantation studies in chicken/quail chimeras utilised the different nucleoli appearance of cells to differentiate different species. Thus transplanation and subsequent histological processing allowed identification of the migration path and final destination of transplanted neural crest cells.
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| Similar later experiments have now been carried out using the neural crest cells molecularly tagged with (LacZ).
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| ==Abnormalities==
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| ===Neuroblastoma===
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| [[File:Neuroblastoma.jpg|thumb|Neuroblastoma]]
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| [[File:Childhood cancer survival rates.jpg|thumb|Childhood cancer survival rates]]
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| [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=256700 OMIM - Neuroblastoma]
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| ===Digeorge Syndrome (DGS)===
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| [[File:Digeorge chromosome22.jpg|thumb|Digeorge chromosome 22]]
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| * DiGeorge syndrome is the most frequent microdeletion syndrome in humans caused by a hemizygous deletion (1.5 to 3.0-Mb) of chromosome 22q11.2.
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| * Velo-cardio-facial syndrome, Hypoplasia of thymus and parathyroids, third and fourth pharyngeal pouch syndrome.
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| * Abnormalities: cardiovascular, thymic and parathyroid, craniofacial anomalies, renal anomalies, hypocalcemia and immunodeficiency.
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| ===Intestinal Aganglionosis===
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| [[File:Megacolon surgery.gif]]
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| [[File:Megacolon stoma.gif]]
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| * Intestinal Aganglionosis, Hirschsprung's Disease or Megacolon
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| * lack of enteric nervous system (neural ganglia) in the intestinal tract responsible for gastric motility (peristalsis).
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| * severity is dependent upon the amount of the GIT that lacks intrinsic ganglia, due to developmental lack of neural crest migration into those segments.
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| * first indication in newborns is an absence of the first bowel movement, other symptoms include throwing up and intestinal infections.
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| * Clinically this is detected by one or more tests (barium enema and x ray, manometry or biopsy) and can currently only be treated by surgery. A temoporary ostomy (Colostomy or Ileostomy) with a stoma is carried out prior to a more permanent pull-through surgery.
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| ===Melanoma===
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| [[File:Melanoma.jpg]]
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| * In Australia each year 8,800 people are diagnosed with melanoma, and almost 1000 people die (Data, Cancer Council Australia).
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| * Two different findings on the reprogramming of melanoma cells, which have a neural crest origin, when transplanted between species into embryos.
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| [http://www.melanoma.com/staging.html Melanoma staging]
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| ===Neurofibromatosis Type 1 (NF1)===
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| * Neurofibromatosis Type 1 (von Recklinghausen) occurs in 1 in 3,000 to 4,000 people with characteristic skin blemishes forming in early childhood.
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| * Multiple ''café-au-lait'' spots (flat skin patches darker than the surrounding area) appear in early childhood which increase in both size and number with age.
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| * tumors can develop along nerves in the skin, brain, and other parts of the body. In the iris of the eye, Lisch nodules (benign growths) also appear
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| :(French, ''café-au-lait'' = coffee with milk)
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| [http://atlasgeneticsoncology.org/Tumors/NeurofibromaID5098.html Atlas of Genetics and Cytogenetics in Oncology- Neurofibroma]
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| == References ==
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| ===Textbooks===
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| * '''The Developing Human: Clinically Oriented Embryology''' (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter Chapter 10 The Pharyngeal Apparatus pp201 - 240.
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| * '''Larsen’s Human Embryology''' by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 12 Development of the Head, the Neck, the Eyes, and the Ears pp349 - 418.
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| ===Online Textbooks===
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| * '''Developmental Biology''' by Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000 [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.section.3109#3133 The Cranial Neural Crest] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.3111 Figure 13.1. Regions of the neural crest] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.3134 Figure 13.7. Cranial neural crest cell migration in the mammalian head] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.3118 Figure 13.2. Neural crest cell migration in the trunk of the chick embryo] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.3138 Figure 13.10. Separation of the truncus arteriosus into the pulmonary artery and aorta] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.5460 Figure 22.23. Chick embryo rhombomere neural crest cells and their musculoskeletal packets] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.3127 Figure 13.4. Segmental restriction of neural crest cells and motor neurons by the ephrin proteins of the sclerotome] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.43 Figure 1.3. Pharyngeal arches] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.table.3135 Table 13.2. Some derivatives of the pharyngeal arches]
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| :Neural Crest Experiments: [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.63 Figure 1.11. Neural crest cell migration Chimera experiment] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.figgrp.3130 Figure 13.5. Pluripotency of trunk neural crest cells]
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| * '''Molecular Biology of the Cell''' Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002 [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.3946 Figure 21-80. The main pathways of neural crest cell migration] [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.3968 Figure 21-91. Diagram of a 2-day chick embryo, showing the origins of the nervous system] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=neural_crest&rid=mboc4.figgrp.3511 Figure 19-23. An example of a more complex mechanism by which cells assemble to form a tissue]
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| * '''Neuroscience''' Purves, Dale; Augustine, George J.; Fitzpatrick, David; Katz, Lawrence C.; LaMantia, Anthony-Samuel; McNamara, James O.; Williams, S. Mark. Sunderland (MA): Sinauer Associates, Inc.; c2001[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=neurosci.figgrp.1449 Figure 22.1. Neurulation in the mammalian embryo] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=neurosci.figgrp.1503 Figure 22.12. Cell signaling during the migration of neural crest cells]
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| * '''Madame Curie Bioscience Database''' Chapters taken from the Madame Curie Bioscience Database (formerly, Eurekah Bioscience Database) [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A53006 Cranial Neural Crest and Development of the Head Skeleton] | [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=ch2957 Neural Crest Cells and the Community of Plan for Craniofacial Development: Historical Debates and Current Perspectives] | [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A63004&rendertype=figure&id=A63009 Figure 1. Diagram of an E10 embryo showing the origins of neural crest cells that colonize the developing gastrointestinal tract]
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| * '''Basic Neurochemistry: Molecular, Cellular, and Medical Aspects''' Siegel, George J.; Agranoff, Bernard W.; Albers, R. Wayne; Fisher, Stephen K.; Uhler, Michael D., editors Philadelphia: Lippincott,Williams & Wilkins; c1999[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=bnchm.figgrp.1881 Figure 27-10. Neuropoietic model of neural crest cell lineage] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=neural_crest&rid=bnchm.figgrp.1883 Figure 27-11. Growth factor control of neural crest lineage decisions] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=neural_crest&rid=bnchm.figgrp.1893 Figure 27-15. The Schwann cell lineage]
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| ===Search ===
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| * '''Bookshelf''' [http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=neural_crest neural crest]
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| * '''Pubmed''' [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=neural_crest neural crest]
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| == UNSW Embryology Links ==
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| * '''Notes:''' [http://embryology.med.unsw.edu.au/Notes/ncrest.htm Introduction] | [http://embryology.med.unsw.edu.au/Notes/ncrest2.htm Abnormalities] | [http://embryology.med.unsw.edu.au/Notes/ncrest3.htm Stage 13/14] | [http://embryology.med.unsw.edu.au/Notes/ncrest4.htm Stage 22] | [http://embryology.med.unsw.edu.au/Notes/ncrest5.htm Stage 22 high power] | [http://embryology.med.unsw.edu.au/Notes/ncrest6.htm Generation] | [http://embryology.med.unsw.edu.au/Notes/ncrest7.htm Migration] | [http://embryology.med.unsw.edu.au/Notes/ncrest8.htm Peripheral Ganglia] | [http://embryology.med.unsw.edu.au/Notes/ncrest9.htm GIT Enteric] | [http://embryology.med.unsw.edu.au/Notes/ncrest12.htm Heart][http://embryology.med.unsw.edu.au/Notes/ncrest10.htm Molecular] | [http://embryology.med.unsw.edu.au/Notes/ncresttxt.htm Text only] | [http://embryology.med.unsw.edu.au/Notes/ncrestlink.htm Web Links]
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| * '''Lectures:''' [http://embryology.med.unsw.edu.au/Science/ANAT2341lecture13.htm ANAT2341 - Embryology 2008 - Lecture 13]
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| * '''Movies:''' [http://embryology.med.unsw.edu.au/Movies/neural.htm#ncrest Neural Movies]
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| == External Links ==
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| '''Research Labs'''
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| * University of Michigan [http://www.biology.lsa.umich.edu/research/labs/ktosney/file/Res/ResNc.html Tosney Lab]
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| * Stowers Institute [http://www.stowers-institute.org/labs/KulesaLab.asp Kulesa Lab] | [http://www.stowers-institute.org/labs/TrainorLab.asp Trainor Lab]
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| * University College London [http://www.anat.ucl.ac.uk/research/mayor/index.html Mayor Lab]
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| * University of Iowa [http://www.anatomy.uiowa.edu/pages/directory/faculty/cornell.asp Cornell Lab]
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| * Washington University in St. Louis, School of Medicine, Department of Pediatrics [http://peds.wustl.edu/research/labs/Heuckeroth_Robert_O/ Heuckeroth Lab]
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| [[Category:Neural Crest]]
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