Differentiation of the Placode Ectoderm Neural Crest Derivatives
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1 Dr. Andrea D. Székely Differentiation of the Placode Ectoderm Neural Crest Derivatives Acknowledgements to Dr Károly Altdorfer Dr Nándor Nagy
2 EARLY DEVELOPMENT The neural crest and craniofacial placodes are two distinct progenitor populations that arise at the border of the vertebrate neural plate. This border region develops through a series of inductive interactions that begins before gastrulation and progressively divide embryonic ectoderm into neural and non-neural regions, followed by the emergence of neural crest and placodal progenitors. Andrew K Groves, Carole LaBonne Setting appropriate boundaries: fate, patterning and competence at the neural plate border. Dev. Biol.: 2014, 389(1);2-12 PubMed
3 C. Milet, A.H. Monsoro-Burq / Developmental Biology 366 (2012) 22 33
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5 PRIMARY NEURULATION Neural induction and neurulation Specification of neural fate and formation of the neural tube. NEURAL INDUCTION : the delineation of ectodermal cells to the neural fate NEURULATION: the process in which the ectoderm of the future brain and spinal cord - the neural plate develops, folds and forms the neural tube
6 default pathway INDUCTION OF THE NEURAL TUBE inhibition of default activin epiblast BMP-2 BMP-4 inhibition of default mesoderm follistatin chordin noggin (BMPinhibition) epidermis E-cadherin N-Cadherin neural tube Numerous signal proteins inhibit the activity of BMP/Activin, thereby maintaining the default mechanism ( neural tube )
7 DIFFERENTIATION Placode: cranial and/or lateral epithelial thickenings may form vesicles Neural crest: caudal and medial region may induce epithelio-mesenchymal transition
8 PLACODE Placodes are localized regions of columnar epithelium that develop from ectoderm between the 10- and 30-somite stage at the border between neural plate/neural crest and the future epidermis.
9 PREPLACODAL DEVELOPMENT MODEL Bmp acts as a morphogen that specifies neural crest (NC) within a narrow but low range of signalling. Changing levels of Bmp do not distinguish preplacodal from epidermal potential. Preplacodal ectoderm (PPE) fate is specified in competent cells near the neural-nonneural border by dorsally expressed Bmp antagonists, Fgf and Pdgf. Complete attenuation of Bmp is required for PPE specification.
10 CRANIAL PLACODES
11 NEUROGENIC PLACODES DORSOLATERAL PLACODES -- trigeminal placode, which consists of ophthalmic and maxillomandibular parts, and gives rise to the cells of the trigeminal ganglion -- otic placode forms the otic pit and the otic vesicle, giving rise eventually to organs of hearing and equilibrium. EPIBRANCHIAL or epipharyngeal placodes generate the distal portion of the ganglia of cranial nerves VII, IX and X: -- geniculate placode, associated with the first branchial cleft generates the geniculate ganglion and distal parts of cranial nerve VII -- petrosal placode, associated with the second branchial cleft generates the glossopharyngeal ganglion, and distal parts of cranial nerve IX -- nodosal placode, associated with the third branchial cleft, generates the nodose ganglion and distal parts of cranial nerve X -- olfactory placode (or nasal placode [) gives rise to the olfactory epithelium NON-NEURAL PLACODES -- lens placode under the direction of the optic vesicle gives rise to the lens of the eye. -- adenohypophyseal placode, which forms the anterior lobe of the pituitary gland.
12 CRANIAL PLACODES Hypophyseal Olfactory Lens Trigeminal Otic Epibranchial Rathke s pouch Adenohypophysis Olfactory epithelium Lens Trigeminal ggl. (partially) Otic vesicle membranous labyrinth, spiral+vestibular ggl(cn8) Epibranchial > taste buds, geniculate ggl.(cn7.), inf ggl (CN9, 10) Neural plate Neural crest Ectoderm CNS Ganglia etc. Epidermis etc.
13 CRANIAL PLACODES IN THE CHICK EMBRYO Neural crest Placode
14 NEURAL CREST 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.
15 THE NEURAL CREST The neural crest is a transient and multipotent cell population arising at the edge of the neural plate in vertebrates. Recent findings highlight that neural crest patterning is initiated during gastrulation, i.e. earlier than classically described, in a progenitor domain named the neural border. The rostral forebrain DOES NOT form neural crest cells
16 DERIVATIVES OF THE NEURAL CREST 1a bipolar neuroblast 1b differentiating neuroblast 1c pseudounipolar sensory neuron 2a unipolar neuroblast 2b vegetative ganglion cells (multipolar) 2c adrenal medulla - chromaffin cells 3a glioblast 3b Schwann cells 3c satellite cells 4a mesenchymal cells 4b leptomeningeal cells 4c ectomesenchymal cells 5 pigment cell 5b melanocyte
17 C. Milet, A.H. Monsoro-Burq / Developmental Biology 366 (2012) 22 33
18 NEURAL CREST INDUCTION MOLECULAR REGULATION ectoderm: BMP, Wnt mesoderm FGF-8 (amphibian data) epidermal ectoderm neural ectoderm neural crest - high concentration of BMP - low concentration of BMP - medium concentration of BMP Msx-1, Pax-3 expression starts (characteristic for NC cells) snail-1 and slug (snail-2) expression is needed for EMT slug is expressed at gastrulation as well Changes in adhesion properties (adhesion molecules)
19 DERIVATIVES OF THE NEURAL CREST Migration into the mesenchymal layer Craniocaudal streams EMT - Epithelial to - mesenchymal transformation Influenced by: ECM molecules, growth factors
20 REGIONS OF THE NEURAL CREST Cranial (caudal to the forebrain until the 6th rhombomere) Vagal (between somites 1-7) Truncal (somites 8-28) Lumbosacral (caudal to somite 29)
21 Rhombomeres 1,2,(3) Rhombomeres (3),4,(5) Rhombomeres (5),6,7,8 NC cell migration in 3 streams: trigeminal around 3 divisions of CN V. (1st branchial arch*+frontonasal process) hyoid into 2. branchial arch postotic (= behind otic vesicle) into branchial arches 3-6. Ectomesenchyme: bones, cartilage, connective tissue, vessels * 2 of 3 auditory ossicles, jaw (Meckel s cartilage)- skull - new head
22 5th and 6th prosomere levels do not give rise to neural crest NC from hindbrain levels colonise the 1st-3rd pharyngeal arches. Each rhombomeric and mesencephalic crest cell remember to the segmental code. In the pharyngeal region, the pathways of crest cell migration are in close relation with HOXb gene expression Cells of the cranial crest may be patterned with level specific instructions, the trunk crest regulation seems to be different.
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24 NEURAL CREST - HEAD REGION NEURAL DERIVATIVES general sensory ganglia - superior ganglia of CN 9 and CN 10 - part of the trigeminal ganglion (+ from placode) autonomic ganglia - ciliary (CN 3) - pterygopalatine, submandibular (CN 7), otic (CN 9) ganglia all from the 2nd rhombomer (arising from the vicinity of CN 5 branches)
25 NEURAL CREST - HEAD REGION ECTOMESENCHYMAL TISSUE bones of the skull (frontal, parietal, temporal squama, nasal, vomer, palatine, maxillae,mandible) meninges (choroid and sclera ) dentin glandular connective tissue (lacrimal, nasal, labial, palatine, oral, salivary, thyroid, parathyroid, thymus) connective tissue of the head (melanocytes, cartilage, ligaments, tendons) conotruncal septum (tunica media of the outflow tract of the heart and the great vessels )
26 NEURAL CREST - TRUNK REGION 1 - cells which migrate through the dorsal pathway, differentiate to melanocytes in the skin and hair follicles 2 - cells which migrate through the ventral pathway may choose between two fatesand take ventrolateral migration between the dermatomyotome and sclerotome cells of the somitesthe form sensory ventrolateral ganglia and migration the accompanying between the glial dermatomyotome satellite cells and Schwann and sclerotome cells (), form sensory ganglia and the accompanying glial satellite cells and Schwann cells ventromedial pathway between sclerotome and neural or take tube the form ventromedial sympathetic pathway and enteric between neurons, sclerotome satellite and neural cells, tube Schwann and form cells, sympathetic and cells and of the enteric adrenal neurons, medulla. satellite cells, Schwann cells, and cells of the adrenal medulla.
27 NEURAL DERIVATIVES OF THE TRUNCAL NEURAL CREST dorsal pathway (1) pigment cells (melanocytes) neural crest dorsal root, cranial nerve sensory ganglia parasympathic and sympathic ganglia mesoderm ventrolateral pathway (2) developing adrenal gland ventromedial pathway(2)
28 NEURAL DERIVATIVES OF THE TRUNCAL NEURAL CREST ventrolateral pathway neural crest Schwann s cells satellite cells unipolar sensory neurons glomus caroticum, parafollicular (C) cells multipolar ganglion cells in sympathetic ganglions FGF, NGF chromaffine cells in adrenal glands prevertebral plexus
29 PERIPHERAL NERVOUS SYSTEM
30 SYMPATHETIC PREVERTEBRAL GANGLIA T1-T4 Superior & middle cervical & stellate ganglion Cardiac and lung plexus T5-L2 Celiac ganglion Sup. mesenteric ggl. Aorticorenal ggl. Inf. mesenteric ggl. Preganglionic fibers Postganglionic fibers
31 MESENCHYMAL DERIVATIVES OF CEPHALIC AND CARDIAC CREST Tissue type Organ, strukture Neurocristopathia Bones Meninges Eye (connective tissue, smooth muscle) Connective tissue Connective tissue of glands frontal, parietal, temporal (squamous part), vomer, nasal, palatine bones, maxilla, mandibula, etc.) pia mater, arachnoidea, dura mater (?) iris (stroma), choroid, ciliary body, sclera, orbit, ciliary muscles cartilages, lihaments, tendons of the head lacrimal, salivary, nasal, palatine, labial, oral glands, thyroid, parathyroid glands, thymus palatine clefts, frontonasal dysplasia, choanal atresia hypertelorism, coloboma, other eye malformations cleft lip DiGeorge syndrome (hypoparathyroidism, immune deficience, thyroid tumors) Teeth odontoblasts (dentin) dental malformations Heart outflow tract, aorticopulmonary septum, tunica media of vessels septum defects, aortic arch defects
32 NEURAL DERIVATIVES OF TRUNCAL AND VAGAL CREST CELLS Organ Cell type Neurocristopathy Cortex of andrenal tumor of adrenal gland or neuroblastoma gland ganglion Cortex of adrenal tumors of chromaffine tissue or phaeochromocytoma gland adrenal gland Skin melanocytes Waardenburg syndrome, albinism Colon (vagal crest) intramural ganglion cells of colon Hirschsprung s disease (megacolon congenita) Small intestine entericus nerve cells, carcinoid tumors (enterochromaffine cells) (Truncal crest) periferal nerves neurofibromatosis (von Recklinghausen s disease)
33 NEURAL AND NON-NEURAL DERIVATIVES OF THE CRANIAL NEURAL CREST
34 DERIVATIVES OF THE NEURAL CREST 1a bipolar neuroblast 1b differentiating neuroblast 1c pseudounipolar sensory neuron 2a unipolar neuroblast 2b vegetative ganglion cells (multipolar) 2c adrenal medulla - chromaffin cells 3a glioblast 3b Schwann cells 3c satellite cells 4a mesenchymal cells 4b leptomeningeal cells 4c ectomesenchymal cells 5 pigment cell 5b melanocyte
35 Thank you for your attention!
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