Lecture - Neural Development

From Embryology

Introduction

Cerebrum development human embryo (week 8, Stage 22)


  1. Understand early neural development.
  2. Understand the formation of the brain; grey and white matter from the neural tube.
  3. Understand the formation of spinal cord.
  4. Understand the role of migration of neurons during neural development.


  • Detailed structure of the adult nervous system is provided in other Anatomy courses.
  • History - Santiago Ramón y Cajal


2016 Lecture PDF

Lecture Resources

Movies  
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 ‎‎Neural Plate
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Neuraltube 001 icon.jpg
 ‎‎Neural Tube
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Secondary neurulation 01 icon.jpg
 ‎‎Secondary Neurulation
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Mouse neural tube 01 movie icon.jpg
 ‎‎Neural Tube Close
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Stage13-CNS-icon.jpg
 ‎‎Stage 13 Neural
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Stage22-CNS-icon.jpg
 ‎‎Stage 22 Neural
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Chicken-neural-crest-migration-01.jpg
 ‎‎Neural Crest 1
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Mouse cranial neural crest migration 01.jpg
 ‎‎Cranial Neural Crest
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Brain fissure development 03.jpg
 ‎‎Sylvian Fissure
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Adult human brain tomography.jpg
 ‎‎Adult Brain
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References  
UNSW Embryology logo
Hill, M.A. (2017). UNSW Embryology (17th ed.) Retrieved September 20, 2017, from https://embryology.med.unsw.edu.au
Neural Links: Introduction | Ventricular System | Stage 22 | Gliogenesis | Fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | Neural Crest | Sensory | Abnormalities | Folic Acid | Iodine Deficiency | Fetal Alcohol Syndrome | Postnatal | Postnatal - Neural Examination | Histology | Historic Neural | Category:Neural
Neural Parts: Introduction | Prosencephalon | Telencephalon | Amygdala | Hippocampus | Basal Ganglia | lateral ventricles | Diencephalon | Epithalamus | Thalamus | Hypothalamus | Pituitary | Pineal | third ventricle | Mesencephalon | Mesencephalon | Tectum | cerebral aqueduct | Rhombencephalon | Metencephalon | Pons | Cerebellum | Myelencephalon | Medulla Oblongata | Spinal Cord | Vascular | Meninges | Category:Neural

Archive: 2015 PDF2014 | 2014 Lecture 19 PDF

Textbook cover The Developing Human, 9th edn.
Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders.
The following chapter links only work with a UNSW connection.
Textbook cover Larsen's human embryology 4th edn.
Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. & Francis-West, P.H. (2009). Larsen's human embryology (4th ed.). New York; Edinburgh: Churchill Livingstone.
UNSW students have full access to this textbook edition through UNSW Library subscription (with student Zpass log-in).
  • Chapter 4 - Fourth Week: Forming the Embryo
  • Chapter 9 - Development of the Central Nervous System
  • Chapter 10 - Development of the Peripheral Nervous System


Early Brain Structure

Primary Vesicles

CNS primary vesicles.jpg

  • rostral neural tube forms 3 primary brain vesicles (week 4)
  • 3 primary vesicles: prosencephalon (forebrain), mesencephalon (midbrain), rhombencephalon (hindbrain)

Brain Flexures

Rapid growth folds the neural tube forming 3 brain flexures

  • cephalic flexure - pushes mesencephalon upwards
  • cervical flexure - between brain stem and spinal cord
  • pontine flexure - generates 4th ventricle

Stage 13 image 098.jpg

Secondary Vesicles

CNS secondary vesicles.jpg

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)


Carnegie stage 13 Embryo showing neural tube and brain flexures.

Neural Tube Primary Vesicles Secondary Vesicles Adult Structures
week 3 week 4 week 5 adult
neural plate
neural groove
neural tube

Brain
Prosencephalon Telencephalon Rhinencephalon, Amygdala, Hippocampus, Cerebrum (Cortex), Hypothalamus, Pituitary | Basal Ganglia, lateral ventricles
Diencephalon Epithalamus, Thalamus, Subthalamus, Pineal, third ventricle
Mesencephalon Mesencephalon Tectum, Cerebral peduncle, Pretectum, cerebral aqueduct
Rhombencephalon Metencephalon Pons, Cerebellum
Myelencephalon Medulla Oblongata
Spinal Cord
Keith1902 fig167.jpg

Historic figure showing the parts derived from the walls of the fore-brain. (After Wilhelm His (1831-1904))

Rhombomeres

  • Hindbrain - Rhombomeres represent the crania-caudal segmentation of the neural tube at the level lot the hindbrain.
  • Historic - Identified morphologically as identifiable regions.
  • Modern - Represent the different expression levels of Hox genes and levels of neural crest migration.
Stage11 historic-Atwell1930-2.jpg Hindbrain neural crest migration.jpg
Historic image of embryonic rhombomeres Hindbrain neural crest migration

Proposed Hox protein classification.jpg

Hox-proteins crania-caudal expression (species comparison)

Neural Layers

Interneuron-radial glial interactions
  • Ventricular Germinal Zone (VGZ) - mitosis at the ventricular luminal surface, produces early-generated macroneurons
  • Subventricular Zone (SVZ) - mitosis away from the ventricular surface, produces later-generated microneurons and glia

Brain

Stage 22 image 150.jpg Stage 22 image 151.jpg
Human Embryo developing head cross section (Week 8, Stage 22) Detail of developing cortex (shown in blue box)
  • Neural progenitor cells migrate from the ventricular layer along radial glia.
  • Cortex layers develops inside (first) outside (last)
  • Glial progenitor cells develop later from the same ventricular stem cells.

Spinal Cord

  • Similar processes to those described for brain.
  • Remember notochord ventral patterning by SHH and dorsal ectoderm (dorsalisation).
  • Identify the different regions within the neural tube (floor plate, basal plate, alar plate, roof plate)
Stage 13 image 057.jpg Stage 22 image 176.jpg
Stage 13 Stage 22
Half of a transverse section of the spinal cord
Bailey406.jpg Bailey407.jpg Bailey408.jpg
Human embryo of 18.5 mm (7.5 weeks). Human embryo of 24 mm (8.5 weeks). Human fetus of about 3 months.
Wilhelm His (1831-1904)

Ventricular Development

Human Embryo (week 8, Stage 22) ventricular system
  • The ventricular system develops from the single cavity formed from the hollow neural tube.
  • This fluid-filled space is separated from the amnion following fusion of the neural tube and closure of neuropores.
  • At different regions sites within the wall (floor of lateral ventricle and roof of the third and fourth ventricles) differentiate to form choroid plexus a modified vascular structure which will produce Cerebrospinal fluid (CSF)
  • choroid plexus is a modified vascular structure which will produce Cerebrospinal fluid (CSF)
Human Fetus (week 10) showing choroid plexus and early ventricular system

(FYI - you do not need to know detailed stage development)

Human Ventricular Development Timeline
  • Stage 11 - appearance of the optic ventricle. The neural groove/tube space is initially filled with amniotic fluid.
  • Stage 12 - closure of the caudal neuropore, onset of the ventricular system and separates the ependymal from the amniotic fluid.
  • Stage 13 - cavity of the telencephalon medium is visible.
  • Stage 14 - cerebral hemispheres and lateral ventricles begin, rhomboid fossa becomes apparent.
  • Stage 15 - medial and lateral ventricular eminences cause indentations in the lateral ventricle
  • Stage 16 - hypothalamic sulcus is evident.
  • Stages 17-18 - interventricular foramina are becoming relatively smaller, and cellular accumulations indicate the future choroid villi of the fourth and lateral ventricles.
  • Stage 18 - areae membranaceae rostralis and caudalis are visible in the roof of the fourth ventricle, and the paraphysis is appearing.
  • Stage 19 - choroid villi are visible in the fourth ventricle, and a mesencephalic evagination (blindsack) is visible
  • Stage 20 - choroid villi are visible in the lateral ventricle.
  • Stage 21 - olfactory ventricle is visible.
  • Stages 21-23 - lateral ventricle has become C-shaped (anterior and inferior horns visible). Recesses develop in the third ventricle (optic, infundibular, pineal).

Data from O'Rahilly R, Müller F., 1990[1]

Cranial Nerves

Keith1902 fig180.jpg

Historic diagram showing the relationship of the Cranial Nerves to the Primitive Segments of the Head.

Fetal Neural

Neural-development.jpg

Timeline of events in Human Neural Development

Brain ventricles and ganglia development 03.jpg

Brain fissure development 02.jpg

During the fetal period there is ongoing growth in size, weight and surface area of the brain and spinal cord. Microscopically there is ongoing: cell migration, extension of processes, cell death and glial cell development.

Cortical maturation (sulcation and gyration) and vascularization of the lateral surface of the brain starts with the insular cortex (insula, insulary cortex or insular lobe) region during the fetal period. This cerebral cortex region in the adult brain lies deep within the lateral sulcus between the temporal lobe and the parietal lobe.

  • sulcation - The process of brain growth in the second to third trimester which forms sulci, grooves or folds visible on fetal brain surface as gyri grow (gyration). Abnormalities of these processes can lead to a smooth brain (lissencephaly).
  • gyration - The development of surface folds on the brain (singular, gyrus)

Insular Gyral and Sulcal Development

  • 13-17 gestational weeks - appearance of the first sulcus
  • 18-19 gestational weeks - development of the periinsular sulci
  • 20-22 gestational weeks - central sulci and opercularization of the insula
  • 24-26 gestational weeks - covering of the posterior insula
  • 27-28 gestational weeks - closure of the laeteral sulcus (Sylvian fissure or lateral fissure)

(Data from[2])

  • Between 29-41 weeks volumes of: total brain, cerebral gray matter, unmyelinated white matter, myelinated, and cerebrospinal fluid (from MRI)
    • grey matter- mainly neuronal cell bodies; white matter- mainly neural processes and glia.
  • 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 [3])


Neural development will continue after birth with substantial glial development, growth, death and reorganization occuring during the postnatally.

Gray0654.jpg Gray0655.jpg Gray0658.jpg
Human brain at three months (median sagittal section) Human brain at four months (inferior surface) Human brain at five months (outer surface)
Links: Neural System - Fetal | Neuroscience - Regional specification of the developing brain

Folate and Neural Development

Folate one-carbon metabolism

Research over the last 20 years had suggested a relationship between maternal diet and the birth of an affected infant. Recent evidence has confirmed that folic acid, a water soluble vitamin (vitamin B9) found in many fruits (particularly oranges, berries and bananas), leafy green vegetables, cereals and legumes, may prevent the majority of neural tube defects.

Required for DNA metabolism in rapidly dividing cells.

USA Statistics

In the U.S.A. the Food and Drug Administration in 1996 authorized that all enriched cereal grain products be fortified with folic acid, with optional fortification beginning in March 1996 and mandatory fortification in January 1998. The data below shows the subsequent changes in anencephaly and spina bifida rate over that period.

USA spina bifida rates.jpgUSA anencephaly rates.jpg


Links: Folic Acid and Neural Tube Defects

Thyroid System and Neural Development

Human thyroid system and neural development.jpg

Timeline of human thyroid system and brain development from conception to birth.[4] (Estimation of neurogenesis adapted from Bayer et al.[5])

Links: Endocrine - Thyroid Development

Environmental Effects and Neural Development

Fetal Alcohol Syndrome (FAS) facial features[6]

The developmental environment can also impact upon neural growth; maternal drugs such as alcohol and heavy metals such as lead (mining, historically both petrol and paint).

Postnatal

Postnatal environment, diet and other sensory abnormalities (hearing) can also impact on achieving developmental milestones.

WHO motor development milestones.jpg

WHO motor development milestones

References

  1. R O'Rahilly, F Müller Ventricular system and choroid plexuses of the human brain during the embryonic period proper. Am. J. Anat.: 1990, 189(4);285-302 PubMed 2285038
  2. A Afif, R Bouvier, A Buenerd, J Trouillas, P Mertens Development of the human fetal insular cortex: study of the gyration from 13 to 28 gestational weeks. Brain Struct Funct: 2007, 212(3-4);335-46 PubMed 17962979
  3. P S Hüppi, S Warfield, R Kikinis, P D Barnes, G P Zientara, F A Jolesz, M K Tsuji, J J Volpe Quantitative magnetic resonance imaging of brain development in premature and mature newborns. Ann. Neurol.: 1998, 43(2);224-35 PubMed 9485064
  4. Kembra L Howdeshell A model of the development of the brain as a construct of the thyroid system. Environ. Health Perspect.: 2002, 110 Suppl 3;337-48 PubMed 12060827
  5. S A Bayer, J Altman, R J Russo, X Zhang Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology: 1993, 14(1);83-144 PubMed 8361683
  6. Daniel J Wattendorf, Maximilian Muenke Fetal alcohol spectrum disorders. Am Fam Physician: 2005, 72(2);279-82, 285 PubMed 16050451


Historic Embryology

Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Images

Text-Book of Embryology - 1921
Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.

The nervous system

} Gray, Henry. Anatomy of the Human Body. Philadelphia: Lea & Febiger, 1918.
Anatomy of the Human Bod - 1918

ANAT2341 Course Timetable  
Week (Mon) Lecture 1 (Mon 1-2pm) Lecture 2 (Tue 3-4pm) Practical (Fri 1-3pm)
Week 2 (1 Aug) Introduction Fertilization Lab 1
Week 3 (8 Aug) Week 1 and 2 Week 3 Lab 2
Week 4 (15 Aug) Mesoderm Ectoderm Lab 3
Week 5 (22 Aug) Early Vascular Placenta Lab 4
Week 6 (29 Aug) Gastrointestinal Respiratory Lab 5
Week 7 (5 Sep) Head Neural Crest Lab 6
Week 8 (12 Sep) Musculoskeletal Limb Development Lab 7
Week 9 (19 Sep) Renal Genital Lab 8
Mid-semester break
Week 10 (3 Oct) Public Holiday Stem Cells Lab 9
Week 11 (10 Oct) Integumentary Endocrine Lab 10
Week 12 (17 Oct) Heart Sensory Lab 11
Week 13 (24 Oct) Fetal Birth and Revision Lab 12

ANAT2341 2016: Moodle page | ECHO360 | Textbooks | Students 2016 | Projects 2016


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Cite this page: Hill, M.A. 2017 Embryology Lecture - Neural Development. Retrieved September 20, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Neural_Development

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