神经嵴细胞和轴突的特异性

1、Neural crest cells and axonal specificity 1. The neural crest and some derivatives of the neural crest 2. The neural crest can be divided into four main functional domains The trunk neural crest The cranial (面部) neural crest The cardiac(心区) neural crest The vagal(迷走) and sacral(尾底) neural crestThe n

2、eural crest cells originate at the dorsalmost region of the neural tubeThe neural crest cells generate a number of differentiated cell types the neurons and glial cells(胶质细胞) of the sensory, sympathetic, and parasympathetic nervous systems the epinephrine-producing (medulla) cells of the adrenal gla

3、nd(肾上腺髓质细胞) the pigment-containing cells of the epidermis many of the skeletal and connective tissue components of the head. Table 13.1Some derivatives of the neural crestPeripheral nervous system (PNS)(外周神经系统)：including sensory ganglia, sympathetic and parasympathetic ganglia, Schwann cells(雪旺细胞),N

4、euroglial cells.Endocrine and paraendocrine derivatives(内分泌和旁分泌组织)：Calcitonin-secreting cells (降血钙素分泌细胞),Carotid body type I cells(颈动脉一型体细胞).Pigment cells(色素细胞)：Epidermal pigment cells.Facial cartilage and bone(面部的骨骼和骨组织)：Facial and anterior ventral skull cartilage and bones.Connective tissue(结缔组织)：

5、Corneal endothelium and stroma,Tooth papillae,Dermis, smooth muscle, and adipose tissue of skin of head and neck, Connective tissue of salivary, lachrymal, thymus, thyroid, and pituitary glands ，Connective tissue and smooth muscle in arteries of aortic arch origin.Regions of the neural crest. The cr

6、anial neural crest migrates into the branchial arches and the face to form the bones and cartilage of the face and neck. It also produces pigment and cranial nerves. The vagal neural crest (near somites 17) and the sacral neural crest (posterior to somite 28) form the parasympathetic nerves of the g

7、ut. The cardiac neural crest cells arise from the neural crest by somites 13; they are critical in making the division beeween the aorta and the pulmonary artery. Neural crest cells of the trunk (about somite 6 through the tail) make the sympathetic neurons, and a subset of these (at the level of so

8、mites 1824) form the medulla portion of the adrenal gland.The trunk neural crestThe mechanisms of trunk neural crest migration1. How is migration initiated? 2. How do the migratory agents know the route on which to travel? 3. What signals indicate that the destination has been reached and that migra

9、tion should end? The neural crest cell migration Neural crest cells originate from the neural folds through interactions of the neural plate with the presumptive epidermis. In cultures of embryonic chick ectoderm, epidermis can induce neural crest formation in the neural plate to which it is connect

10、ed. These can be mimicked by culturing neural plate cells with bone morphogenetic proteins(骨形态发生蛋白) 4 and 7(BMP4 and BMP7), two proteins that are known to be secreted by the presumptive epidermis. BMP4 and BMP7 induce the expression of the Slug protein and the RhoB protein in the cells destined to b

11、ecome neural crest The RhoB protein may be involved in establishing the cytoskeletal conditions that promote migration. The Slug protein is to activate the factors that dissociate the tight junctions between the cells. N-cadherin is expressed before the neural crest cells migration from the neural t

12、ube. this cell adhesion protein is downregulated at the time of cell migration ,but they begin to express it again as they aggregate to form the dorsal root and sympathetic ganglia. All migrating neural crest cells express HNK-1 (red stain), as in Figure 13.2. The RhoB protein (green stain) is expre

13、ssed in cells as they leave the neural crest.Cells expressing both HNK-1 and RhoB appear yellow.Recognition of surrounding extracellular matrices The extracellular matrix molecules that enable or forbid migration.(这两类分子通过不同区域分布确定迁移路线) These proteins promotes migration include fibronectin, laminin, v

14、arious collagen molecules(胶原分子), and proteoglycans蛋白聚糖. Another proteins impedes migration(the ephrin proteins). These proteins are expressed in the posterior section of each sclerotome, and wherever they are, neural crest cells do not go The neural crest cells recognize the ephrin proteins through

15、their cell surface Eph receptors. Binding to the ephrins activates the tyrosine kinase(酪氨酸激酶)domains of the Eph receptors . these kinases probably phosphorylate proteins that interfere with the actin cytoskeleton that is critical for cell migration. Chemotactic(趋化) and maintenance(维持) factors are al

16、so important in neural crest cell migration. Stem cell factor is critical in allowing the neural crest cells that enter the skin, and it may also serve as an anti-apoptosis(抗凋亡) factor and a chemotactic factor. If stem cell factor is secreted from cells that do not usually synthesize this protein (s

17、uch as the cheek epithelium or footpads), neural crest cells will enter those regions and become melanocytes .Segmental restriction of neuralcrest cells and motor neurons by the ephrin proteins of the sclerotome. (A) Negative correlation between regions of ephrin in the sclerotome (dark blue stain,

18、left) and neural crest cell migration (green HNK-1 stain, right). (B) When neural crest cells are plated on fibronectin-containing matrices with alternating stripes of ephrin, they bind to those regions lacking ephrin. (C) Composite scheme showing migration of spinal cord neural crest cells and moto

19、r neurons through the ephrin-deficient anterior regions of the sclerotomes. (For clarity, the neural crest cells and motor neurons are each depicted on only one side of the spinal cordThe pluripotency of trunk neural crest cells A single neural crest cell can differentiate into any of several differ

20、ent cell types,depending on its location within the embryo. For example, the parasympathetic neurons formed by the vagal (neck) neural crest cells produce acetylcholine(乙酰胆碱) . The sympathetic neurons formed by the thoracic (chest) neural crest cells produce norepinephrine(肾上腺素). But when chick vaga

21、l and thoracic neural crests are reciprocally transplanted, depending on its new location . The pluripotency of some neural crest cells is such that even regions of the neural crest that never produce nerves in normal embryos can be made to do so under certain conditions. Cranial neural crest cells

22、is transplanted into the trunk region, it can form Dorsal root sensory neurons. Pluripotency of trunk neural crest cells. (A) A single neural crest cell isinjected with highly fluorescent dextran(荧光右旋糖酐) shortly before migration of the neural crest cells is initiated. The progeny of this cell will e

23、ach receive some of these fluorescent molecules. (B) Two days later, neural crest-derived tissues contain dextran-labeled cells descended from the injected precursor. The figure summarizes data from two different experiments (case 1 and case 2).The transcription factor plays an important part desing

24、ing the fate of the neural crest cells. The sensory neurons from the neural crest are specified by the transcription factor Neurogenin. The sympathetic and parasympathetic neurons from the neural crest are specified by the related transcription factor Mash-1. The expression of the transcription fact

25、or is seen almost immediately after the neural crest cells emigrate from the neural tube. Final differentiation of the trunk neural crest cells. The final differentiation of neural crest cells is determined in large part by the environment to which they migrate. Heart cells, for example, secrete a p

26、rotein, leukemia inhibition factor (LIF), that can convert adrenergic sympathetic neurons into cholinergic neurons without affecting their survival or growth . BMP2, a protein secreted by the heart, lung, and dorsal aorta, influences neural crest cells to differentiate into cholinergic neurons. Anot

27、her paracrine factor, endothelin-3, appears to stimulate neural crest cells to become melanocytes in the skin and adrenergic neurons. The neural crest cells entering the skin also encounter Wnt proteins that inhibit neural development and promote melanocyte differentiation Final differentiation of a

28、 trunk neural crest cell committed to become either an adrenomedullary cell or a sympathetic neuron. Glucocorticoids(糖皮质激素) appear to act at two places in this pathway: first, they inhibit the actions of those factors that promote neuronal differentiation, and second, they induce those enzymes chara

29、cteristic of the adrenomedullary cells. Those cells exposed sequentially to FGF2(碱性成纤维细胞生长因子)and nerve growth factor (NGF) differentiate into the sympathetic neurons.The Cranial Neural Crest Cranial neural crest cells can form melanocytes, neurons, and glia.The major characteristic to produce cartil

30、age and bone. If transplanted into the trunk region, the cranial neural crest participates in forming trunk cartilage. The face is largely the product of the cranial neural crest, and the evolution of the jaws, teeth, and facial cartilage. The chick cranial neural crest cells migrate from the anteri

31、or of hindbrain to rhombomere 6, taking one of three major pathways. First, cells from rhombomeres 1 and 2 migrate to the first pharyngeal arch, forming the jawbones(下颌骨) ,the incus(砧骨) and malleus(锤骨) bones of the ear. They are also pulled by the expanding epidermis to form the frontonasal(前鼻突) pro

32、cess. The neural crest cells of the frontonasal process generate the bones of the face. Second, cells from rhombomere 4 populate the second pharyngeal arch forming the hyoid cartilage of the neck. Third, cells from rhombomere 6 migrate into the third and fourth pharyngeal arches and pouches to form

33、the thymus(胸腺), parathyroid(甲状腺), and thyroid glands(甲状旁腺). Neural crest cells from rhombomeres 3 and 5 do not migrate through the mesoderm surrounding them, but enter into the migrating streams of neural crest cells on either side of them. Cranial neural crest cell migration in the mammalian head.

34、It appears that the combinations of Hox geen expressed in the various regions of neural crest cells specify their fates. When Hoxa-2 is knocked out from mouse embryos, the neural crest cells of the second pharyngeal arch are transformed into those structures of the first pharyngeal arch. Knocked out

35、 the Hoxa-3 gene from inbred mice and found that these mutant mice had severely deficient or absent thymuses, thyroids(甲状腺), and parathyroid glands. Hoxa-1 and Hoxb-1 are both required for the migration of rhombomere 4 neural crest cells into the second pharyngeal pouch. Retinoic acid(维甲酸) induces t

36、he shifting expression of Hox genes , cause rhombomeres 2 and 3 to assume the identity of rhombomeres 4 and 5. Once in the pharyngeal arches and pouches, the neural crest cells have to continue proliferating(增殖) and then differentiate. Mice that are deficient in the gene for endothelin-1 have specif

37、ic abnormalities of pharyngeal arches 3 and 4 ,the neural crest cells enter the arches but are not stimulated to divide . Altering Hox gene expression patterns alters neural crest cell specification.The Cardiac Neural Crest The heart originally forms in the neck region, directly beneath the pharynge

38、al arches. The caudal(尾部) region of the cranial neural crest is sometimes called the cardiac neural crest, since its cells can generate the septum between the aorta and the pulmonary artery .In the chick, the cardiac neural crest lies above the neural tube region from rhombomere 7 through the portion of the third somite, and its cells migrate into pharyngeal arches 3, 4, and 6. the cardiac neural crest is alread