Neural development & neurogenesis

1. Neural development &neurogenesis Dr. Suman Pd. Adhikari

2. Early development • Zygote to 8 cells • Morula (16-64 cell stage) • Blastula / Blastocyst • Gastrula

3. Early Differentiation During early development-3 weeks after conception, the human embryo has divided into three germ layers: Ectoderm Mesoderm Endoderm Inducing factors differentiate the ectoderm layer into skin and nervous tissue

4. Overview of nervous system development • Nervous system starts forming immediately after the primitive gut invaginates the embryonic ball of cells known as blastula • Several principles guide the neural development • 1st: Different brain regions and neuron populations are generated at distinct times of development and exhibit specific temporal schedules • 2nd : Sequence of cellular process comprising ontogeny predicts that abnormalities in early events leads to differences in subsequent stages • 3rd: Specific molecular signals , extracellular growth factors and cognate receptors or transcription factors play roles at multiple stages of development • ILGF • BDNF

5. neurogenesis • Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. • Neurogenesis is responsible for populating the growing brain with neurons. • Recently neurogenesis was shown to continue in several small parts of the brain of mammals: the hippocampus and the sub ventricular zone Stem cells Neural Progenitors Neurons

6. Neurogenesis contd…. • The neural plate forms after gastrulation is completed. • During the third week of gestation the notochord sends signals to the overlying ectoderm, inducing it to become neuroectoderm. • This results in formation of neural plate • Prior to induction cells are undifferentiated (able to be transplanted to a new site)---stem cells • After induction, cells are destined to become a neuron

7. Organizing centers for neurogenesis • Spemann’s organizer (dorsoblastopore lip) • Hensen’s node (similar to Spemann’s org) • Roofplate and notochord become organizers • Secondary organizers: • Isthmic organizer (IsO) • Anterior neural ridge (ANR) • Cortical hem Spemann

8. Neural plate appears Primitive streak appear Edges of Neural plate elevate Edges of Neural plate fuse Neural tube formed NEURULATION (3-4 WEEKS)

9. Neural plate Neural groove Neural tube

10. Neural crest cells derive from the edges of the neural plate and dorsal neural tube • Cells migrate dorso-laterally to form melanocytes and ventro-medially to form dorsal root sensory ganglia and sympathetic chains of the peripheral nervous system and ganglia of the enteric nervous system • Also gives rise to diverse tissues including cells of neuroendocrine, cardiac, mesenchymal, and skeletal systems, forming the basis of many congenital syndromes involving brain and other organs

11. Another non neuronal structure of mesodermal origin formed during neurulation is the notochord found on the ventral side of the neural tube • Notochord plays a critical role during neural tube differentiation • It is a signaling source of soluble growth factors, such as sonic hedgehog (Shh), which impact gene patterning and cell determination Notochord

12. Neural Proliferation • After the neural tube is formed, the developing nervous system cells rapidly increase in number • Cell division occurs in the ventricular zone of the neural tube; when they leave the cell division cycle, cells migrate into other layers Ventricular Zone

13. Neural tube Pial surface of neural tube Marginal zone Ventricular Zone Cell division occur here

14. Regional Differentiation • After closure, neural tube expands differentially to form major morphological subdivisions • Proliferation depends on soluble growth factors made by proliferating cells themselves or released from regional signaling centers • The neural tube can be described in 3 dimensions: • Longitudinal • Circumferential • Radial

15. Longitudinal dimension reflects the rostrocaudal (anterior–posterior) organization --consists of brain and spinal cord. • Circumferential dimension, tangential to the surface, represents two major axes: dorso-ventral axis (cell groups are uniquely positioned from top to bottom) & medial to lateral axis • Finally, radial dimension represents organization from innermost cell layer adjacent to the ventricles to outermost surface

16. 4 weeks 5 weeks Five-vesicle state Three-vesicle state

17. In spinal cord, the majority of tissue comprises lateral plates, which later divide into dorsal or alar plates-composed of sensory interneurons and motor or basal plates-consisting of ventral motor neurons. • Floor plate, in response to Shh from the ventrally located notochord, produces its own Shh, which in turn induces neighboring cells in to express region-specific transcription factors that specify cell phenotype and function.

18. Shh activity in the ventral neural tube (blue dots) is distributed in a ventral-high, dorsal-low profile within the ventral neural epithelium. T.M. Jessell, 2000 Shh activity

19. 3 vesicle stage 5 vesicle stage Neural tube

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