Neural System Development: Difference between revisions

From Embryology
Line 11: Line 11:
* Development of the neural crest and sensory systems (hearing/vision/smell) are only introduced in these notes and are covered in other notes sections.
* Development of the neural crest and sensory systems (hearing/vision/smell) are only introduced in these notes and are covered in other notes sections.


:{{Template:Neural Links}}
:{{Template:Neural Links}} | [http://embryology.med.unsw.edu.au/Notes/neuron.htm original Neural page] | [http://embryology.med.unsw.edu.au/Notes/ncrest.htm original Neural Crest page] | [http://embryology.med.unsw.edu.au/Notes/senses.htm original Sensory page]
 


:{{Template:Systems}}
:{{Template:Systems}}

Revision as of 10:00, 22 May 2010

Stage10 sem6.jpg

Introduction

Neural groove closing to neural tube, early week 4
(Stage 10)

Neural development is one of the earliest systems to begin and the last to be completed after birth. This development generates the most complex structure within the embryo and the long time period of development means in utero insult during pregnancy may have consequences to development of the nervous system.

The early central nervous system begins as a simple neural plate that folds to form a groove then tube, open initially at each end. Failure of these opening to close contributes a major class of neural abnormalities (neural tube defects).

Within the neural tube stem cells generate the 2 major classes of cells that make the majority of the nervous system : neurons and glia. Both these classes of cells differentiate into many different types generated with highly specialized functions and shapes. This section covers the establishment of neural populations, the inductive influences of surrounding tissues and the sequential generation of neurons establishing the layered structure seen in the brain and spinal cord.

  • Neural development beginnings quite early, therefore also look at notes covering Week 3- neural tube and Week 4-early nervous system.
  • Development of the neural crest and sensory systems (hearing/vision/smell) are only introduced in these notes and are covered in other notes sections.
Neural Links: ectoderm | neural | neural crest | ventricular | sensory | Stage 22 | gliogenesis | neural fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | neural abnormalities | folic acid | iodine deficiency | Fetal Alcohol Syndrome | neural postnatal | neural examination | Histology | Historic Neural | Category:Neural

| original Neural page | original Neural Crest page | original Sensory page


System Links: Introduction | Cardiovascular | Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Immune | Integumentary | Musculoskeletal | Neural | Neural Crest | Placenta | Renal | Respiratory | Sensory | Birth

--Mark Hill 10:09, 22 April 2010 (EST) Page content from original site and currently being updated and reformatted.

Some Recent Findings

Reading

  • Human Embryology (3rd ed.) Chapter 5 p107-125
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 18 p451-489
  • Essentials of Human Embryology Larson Chapter 5 p69-79
  • Before We Are Born (5th ed.) Moore and Persaud Chapter 19 p423-458
  • Human Embryology, Fitzgerald and Fitzgerald
  • History of Science- Brain and Mind, Brain Structure, Camille Golgi, S. Ramon y Cajal

Objectives

  1. Understand early neural development.
  2. Understand the formation of spinal cord.
  3. Understand the formation of the brain; grey and white matter from the neural tube.
  4. Understand the role of migration of neurons during neural development.
  5. To know the main derivatives of the brain vesicles and their walls.
  6. To know how the nervous system is modelled, cell death etc.
  7. To understand the contribution of the neural crest.
  8. Understand the developmental basis of certain congenital anomalies of the nervous system, including hydrocephalus, spina bifida, anencephaly and encephalocele.

Animal Neural Development

A number of different animal models of neural development, both normal and abnormal, have been established.

Links: Mouse | Pig | Rabbit

Human Early Neural Development

The stages below refer to specific Carneigie stages of development. Data and text modified from O'Rahilly and Müller 1994.[1]

  • stage 8 (about 18 postovulatory days) neural groove and folds are first seen
  • stage 9 the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open.
  • stage 10 (two days later) neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm
  • stage 11 (about 24 days) the rostral (or cephalic) neuropore closes within a few hours; closure is bidirectional, it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently.
  • stage 12 (about 26 days) The caudal neuropore takes a day to close
    • the level of final closure is approximately at future somitic pair 31
    • corresponds to the level of sacral vertebra 2
  • stage 13 (4 weeks) the neural tube is normally completely closed

Secondary neurulation begins at stage 12

  • is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate.

Development Overview

Neuralation begins at the trilaminar embryo with formation of the notochord and somites, both of which underly the ectoderm and do not contribute to the nervous system, but are involved with patterning its initial formation.

Notochord

  • forms initially as the Axial Process, a hollow tube which extends from the primitive pit , cranially to the oral membrane
  • the axial process then allow transient communication between the amnion and the yolk sac through the neuroenteric canal.
  • the axial process then merges with the Endodermal layer to form the Notochordal Plate.
  • the notochordal plate then rises back into the Mesodermal layer as a solid column of cells which is the Notochord.

Ectoderm

  • 2 parts
  • midline neural plate
    • columnar
  • lateral surface ectoderm
    • cuboidal
    • sensory placodes
    • epidermis of skin, hair, glands, ant. pituitary, teeth enamel

Neural Plate

  • extends from buccopharyngeal membrane to primitive node
  • forms above notochord and paraxial mesoderm
  • neuroectodermal cells
    • broad brain plate
    • narrower spinal cord
  • 3 components form: floor plate, neural plate, neural crest

Neural Determination- Neural Plate

  • neuronal populations are specified before plate folds
    • signals from notochord and mesoderm
    • secrete noggin, chordin,follistatin
  • all factors bind BMP-4 an inhibitor of neuralation
    • bone morphogenic protein acts through membrane receptor Neural Determination- Neural populations
  • neuronal populations are also specified before plate folds
  • lateral inhibition generates at spinal cord level 3 strips of cells
  • expression of delta inhibits nearby cells, which express notch receptor, from becoming neurons
  • Delta-Notch- generates Neural strips

Neural Groove

  • forms in the midline of the neural plate (day 18-19)
  • either side of which are the neural folds
  • continues to deepen until about week 4
  • neural folds begins to fuse
  • at 4th somite level

Neural Tube

    • fusion of neural groove extends rostrally and caudally
    • begins at level of 4th somite
    • "zips up" neural groove
    • leaves 2 openings at either end- Neuropores
    • forms the brain and spinal cord Secondary Neuralation
    • caudal end of neural tube formed by secondary neuralation
    • develops from primitive streak region
    • solid cord canalized by extension of neural canal
    • mesodermal caudal eminence Neuropores
    • cranial neuropore closes before caudal
    • failure to close- Neural Tube Defects (NTD)
    • severity dependent upon level, spina bifida anancephaly (More? [neuron2.htm Neural Abnormalities])
    • found that supplementation of maternal diet with folate reduces incidence of NTDs
    • A randomised controlled trial conducted by the Medical Research Council of the United Kingdom demonstrated a 72% reduction in risk of recurrence by periconceptional (ie before and after conception) folic acid supplementation (4mg daily).
    • Women who have one infant with a neural tube defect have a significantly increased risk of recurrence (40-50 per thousand compared with 2 per thousand for all births)

Neural Crest

(More? Neural Crest Development)

  • a population of cells at the edge of the neural plate that lie dorsally when the neural tube fuses
  • dorsal to the neural tube, as a pair of streaks
  • pluripotential, forms many different types of cells
  • cells migrate throughout the embryo
  • studied by quail-chick chimeras
  • transplanted quail cells have obvious nucleoli compared with chicken Neural Crest Derivitives
    • dorsal root ganglia
    • autonomic ganglia
    • adrenal medulla
    • drg sheath cells, glia
    • pia-arachnoid sheath
    • skin melanocytes
    • connective tissue of cardiac outflow
    • thyroid parafollicular cells
    • craniofacial skeleton
    • teeth odontoblasts

Early Brain Structure- 3 primary vesicles

    • rostral neural tube forms 3 primary brain vesicles (week 4)
    • prosencephalon (forebrain)
    • mesencephalon (midbrain)
    • rhombencephalon (hindbrain) Early Brain Structure- 5 secondary vesicles
      From the 3 primary vesicles developing to form 5 secondary vesicles
    • prosencephalon
    • telencephalon (endbrain, forms cerebral hemispheres)
    • diencephalon (betweenbrain, forms optic outgrowth)
    • mesencephalon
    • rhombencephalon- metencephalon (behindbrain), myelencephalon (medullabrain)

Ventricles

(More? [neuron6.htm Notes Chorioid Plexus])

    • cavity within tube will form the contiguious space of the ventricules of the brain and central canal of spinal cord
    • this space is filled initially with amniotic fluid, later with CerebroSpinal Fluid (CSF)
    • CSF is secreted by a modified vascular structure, the [neuron6.htm Chorioid Plexus], lying within the ventricles Brain Flexures
    • rapid growth folds the neural tube forming 3 brain flexures
    • cervical flexure - between brain stem and spinal cord
    • midbrain flexure - pushes mesencephalon upwards
    • pontine flexure - generates 4th ventricle

Neural Layers

    • neural stem cells lie in the layer closest to the ventricular space, the ventricular layer
    • this layer generates both neuroblasts and glioblasts
    • neuroblasts arise first and migrate along radial gial
    • their migration stops at cortical plate

Spinal Cord Axes

    • Experimental manipulation of interactions.
    • Initial experiments looked at how isolated tissues may influence the development of the spinal cord.
    • Repositionining of specific tissues both in vivo and in vitro
    • specific markers of or alteration of differentiation.

Notocord Induction

    • Ventral- Sonic Hedgehog
    • notochord secretes sonic hedgehog
    • Gene expression studies (ISH) showed shh gene expression occured in a subset of inducing tissues
    • has a patterning role elsewhere (limb, sclerotome, lung)
    • 2 signaling activities acting (locally and at a distance) Ventral- Sonic Hedgehog
    • Binds to cell surface receptor patched
    • without shh, patched (Ptc) binds smoothened (Smo)
    • with shh shh-Ptc releases Smo activating G protein pathway

Gene Diseases

  • shh Human mutation- holoprosencephaly 3
    • characteristic facies of the severe form of HPE which included a single fused eye (cyclopia) and a nose-like structure (proboscis) above the eye
    • Downstream targets of Sonic hedgehog signalling: transcription factors like Gli3 (responsible for Greigs polycephalosyndactyly in humans), d Hoxd13 (responsible for polysyndactyly)

Dorsal

    • Dorsalin, growth factor controls patterning in embryonic mesoderm (frog)
    • Transforming Growth factor beta, (TGF b), related factors BMP-2, BMP-4, BMP-7, radar (flies related protein determines dorsoventral)
    • homology search of vertebrate library identified protein of same family.
    • dorsalin-1 (dsl-1) Basler, Cell 73, p687, 1993 Dorsalin-1
    • From overlying ectoderm
    • Naming comes from the obvious reason that it promotes the differentiation of neural crest cells.
    • Also signal for dorsal signal of neural tube.
    • Inhibits the differentiation of motoneurons.
    • Implication is that dsl-1 and shh act antagonistically, or competitively to establish d-v axis of neural tube. Rostro-Caudal Axis
    • What about the third pattern axis?
    • Brain rostro-caudal axis is generated by differential expression of Hox genes (transcriptional activators)
    • corresponding to genetic order on chromosome.
    • Wilkinson, Nature, 341, p405, 1989. Hox Genes
    • Stands for Homeobox domain Genes
    • A family of transcription factors
    • Discovered in flies and conserved between all species.(antennapedia)
    • Expressed in sequence along the embryo rostro-caudal axis.
    • Regulate many other aspects of development.
    • 180aa region binds DNA and regulate gene expression
    • large family of genes organized and expressed in sequence on the chromosome
    • Nkx-2.2 first detected at 1 somite stage
    • Lim hox gene expressed at spinal cord level

Early Development and Neural Derivatives

    • bilaminar embryo- hyoblast
    • trilaminar embryo then ectoderm layer, neural plate, neural groove, neural tube and neural crest
    • cranial expansion of neural tube- central nervous system
    • caudal remainder of neural tube- spinal cord
    • neural crest
    • dorsal root ganglia
    • parasympathetic / sympathetic ganglia.
    • ectodermal placodes- components of the special senses: otic placode (otocyst), nasal placode, lens placode File:Image 002.gif

Neural tube and Genes: neural specification- Notch/Delta, patched receptor. Border- fibroblast growth factor (fgf), BMP (BMP4, msx1) Rostral border- Dlx5

Neural tube patterning

    • segmented along its length- Hox/Lim gene expression
    • ventral identity- sonic hedgehog, BMP7/chordin interaction
    • dorsal identity- dorsalin

Late Neural Development

Three-dimensional magnetic resonance imaging and image-processing algorithms have been used to quantitate between 29-41 weeks volumes of: total brain, cerebral gray matter, unmyelinated white matter, myelinated, and cerebrospinal fluid (grey matter- mainly neuronal cell bodies; white matter- mainly neural processes and glia). A study of 78 premature and mature newborns showed that total brain tissue volume increased linearly over this period at a rate of 22 ml/week. Total grey matter also showed a linear increase in relative intracranial volume of approximately 1.4% or 15 ml/week. The rapid increase in total grey matter is mainly due to a fourfold increase in cortical grey matter. Quantification of extracerebral and intraventricular CSF was found to change only minimally. (text modified from Huppi etal., (1998) Quantitative magnetic resonance imaging of brain development in premature and mature newborns.Ann Neurol 43(2):224-235.) Late Neural Development

Gliogenesis and Myelination

Glial cells have many different types and roles in central and peripheral neural development, though they are typically described as "supportive", and have the same early embryonic origins as neurons. (More? [neuron7.htm Gliogenesis and Myelination])

Early in neural development a special type of developmental glia, radial glia, provide pathway for developing neuron (neuroblasts) migration out from the proliferating ventricular layer and are involved in the subsequent lamination and columnar organization of the central nervous system.

Types of glia: radial glia, astroglia, oligodendroglia, microglia and Schwann cells.

References

  1. Neurulation in the normal human embryo. O'Rahilly R, Müller F. Ciba Found Symp. 1994;181:70-82; discussion 82-9. Review. PMID: 8005032


Journals

Developmental Brain Research Content Listing

Neural Development Welcome to Neural Development | Pubmed Central Volume 1 2006 | Pubmed Central Volume 2 2007 |

International Journal for Developmental Neuroscience Official Journal of the International Society for Developmental Neuroscience |

Developmental Neuroscience Journal Homepage | Hippocampal Development | Vol. 29, No. 3, 2007 |

Neuroscience Official journal of The International Brain Research Organisation (IBRO)

Neuron Neuroscience journal published by Cell press

Online Textbooks

Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. Formation of the Neural Tube | Differentiation of the Neural Tube | Tissue Architecture of the Central Nervous System | Neuronal Types | Snapshot Summary: Central Nervous System and Epidermis

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 Early Brain Development | Construction of Neural Circuits | Modification of Brain Circuits as a Result of Experience

Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. Neural Development | The three phases of neural development

Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct. Developmental Disorders Associated with Failure to Thrive

Search NLM Online Textbooks- "neural development" : Developmental Biology | The Cell- A molecular Approach | Molecular Biology of the Cell | Endocrinology

Reviews

  • The cell biology of neurogenesis. Gotz M, Huttner WB Nat Rev Mol Cell Biol. 2005 Oct;6(10):777-88. PMID: 16314867

Articles

Search PubMed

Search Pubmed: Neural System Development

System Links: Introduction | Cardiovascular | Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Immune | Integumentary | Musculoskeletal | Neural | Neural Crest | Placenta | Renal | Respiratory | Sensory | Birth

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2024, April 30) Embryology Neural System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_System_Development

What Links Here?
© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G