Embryology 4 Neurulation formation of the neural tube

Embryology 4. Neurulation: formation of the neural tube Dr. Nandor Nagy Semmelweis University

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 (neural folds) and forms the neural tube.

Figure 5 -12 Relationships between the neural plate and primitive streak. A, Day 15. B, Day 18. C, Day 19. D, Days 20 to 21. Downloaded from: Student. Consult (on 8 February 2011 04: 03 PM) © 2005 Elsevier

Induction Inductive effects The Nobel Prize in Physiology or Medicine 1935 was awarded to Hans Spemann "for his discovery of the organizer effect in embryonic development".

Induction of the Neural Tube epiblast BMP-2 BMP-4 follistatin chordin noggin (BMPinhibition) N-Cadherin default pathway inhibition of activin default mesoderm inhibition of default epidermis E-cadherin neural tube Numerous signal proteins inhibit the activity of BMP/Activin, thereby maintaining the default mechanism (- neural tube).

Closure of the neural tube in a „zip-lock” like manner Figure 6 -1 Early stages in the formation of the human central nervous system. A, At 18 days. B, At 20 days. C, At 22 days. D, At 23 days. Downloaded from: Student. Consult (on 8 February 2011 04: 16 PM) © 2005 Elsevier

neuroporus anterior Neural tube 3 week old human embryo (2 mm)

Secondary neurulation Condensing mesenchymal cells cavitation Neural tube Tail bud vulnerable target for neural tube defects !

(NTD, neural tube defects) Aproximately 1: 1000 infants with spina bifida occure

Non-closure of neural tube anomalies: spina bifida Hair Open neural tube Meninx Skin Transverse process Rachisis Spina bifida occulta (skin-covered NTDs) Spinal cord Meninx Meningocele Meningomyelocele 15

Meningomyelokele, spina bifida (neuroporus posterior is open) : Open NTDs occur in about 0. 1% of all live births

Non-Closure of Neural Tube Hole on cranial bone Meninges Anencephalia Ventricle Bulging brain tissue Pax 3 teratogenic effects sonic hedgehog e. g. : maternal diabetes hyperthermia openbrain protective factors Folic acid, B 12 17

-Folate acid (vitamin B 9) supplementation (400 micrograms of synthetic folic acid per day in a prenatal multivitamin) can reduce the incidence of NTDs by up to 75%. Folic-acid receptor expression in human embryo

Neural crest cells are a unique population of cells that arise from the dorsal part of the forming neural tube during neurulation and gives rise to a diverse cell lineage including : myofibroblasts, cartilage, bone, melanocytes, endocrine cells, peripheral neurons, glial cells. 3 weeks old human embryo

The NC cells undergo an epithelial-to-mesenchymal transformation as they detach from the neural tube.