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Lecture 5: Neurulation Seung K. Kim Dept. of Developmental Biology DB201 Development & Disease Mechanisms . Summary of cell movements in gastrulation Mitchell and Sharma, Embryology, An Illustrated Colour Text 2005) Formation of the primitive streak Lodish, Molecular Cell Biology 2006 • • • Establishing bilateral symmetry Beginning of A-P axis Initiating formation of endoderm and mesoderm and ectoderm The node breaks bilateral symmetry to form the L-R axis Figure 22-87a Molecular Biology of the Cell (© Garland Science 2008) Sagittal schematic of human gastrula Langman’s Medical Embryology 11th Edition Fates of different mesoderm subdivisions Dorsal Ventral Neurulation Neurulation • Neurulation refers to the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube. The embryo at this stage is termed the neurula. • Begin the patterning of neural differentiation along the D-V, A-P and radial (proximo-distal) axes • Create and disseminate neural crest cells • Later, establish the important architectural features of the hindmid- and forebrain, with closure of the neural tube Stages of spinal cord development in neurulation From Jessel, Nature Reviews Genetics Copp et al 2003 Nature Reviews Genetics Figure 22-79 Molecular Biology of the Cell (© Garland Science 2008) Overview of neural tube development and closure Central nervous system function is required for ingestion of amniotic fluid, a biomarker Normal amniotic fluid levels on trans-abdominal ultrasound Polyhydramnios on trans-abdominal ultrasound Neural tube defects Development of dorsal-ventral asymmetry in neurogenesis Primitive streak regression and notochord growth Possible modes of inductive signaling Dorsal ventral polarization in fetal spinal cord architecture Dorsal root ganglion [DRG] sensory neurons, commisural [C] and accessory neurons [A] are dorsal Motor neurons [M] and ventral interneurons [V] are ventral From Jessel, Nature Reviews Genetics Sonic hedgehog (Shh) is a morphogen produced in the notochord and floor plate Jessel, Nature Reviews Genetics Figure 22-80a Molecular Biology of the Cell (© Garland Science 2008) Figure 22-80 Molecular Biology of the Cell (© Garland Science 2008) Fates of different mesoderm subdivisions Dorsal Ventral Regulation of somite differentiation along the dorsal ventral axis. Arrows show known signals controlling somite cell fates, including Sonic hedgehog (Shh) and neurotrophin 3 (NT-3) and Wnt from the ‘roof plate’ of the neural tube. The later fates of subsets of some somite cells are also shown. We will see in the next lecture how the notochord is an organizer of neural development. Development of anterior-posterior asymmetry in neurogenesis Note: A-P = rostral-caudal HOX genes and establishment of anterior-posterior polarity Figure 22-46 Molecular Biology of the Cell (© Garland Science 2008) Figure 22-97 Molecular Biology of the Cell (© Garland Science 2008) Hox genes regulate neural crest cell migration into the arches We will see this again when we cover head and neck development in a later lecture Neural crest cells and progeny migrate and populate diverse tissues and organs Neural crest cell lineage and progeny Gilbert, Developmental Biology, 2009 Waardenburg syndrome from mutations in Pax3, a transcription factor in neural crest cells 1. Skin: Partial albinism 2. Hair: White forelock, white eye lashes, premature graying of hair (sometimes called ‘Piebaldism’ 3. Eyes: Laterally displaced inner canthi 4. Ears: Cochlear deafness 5. Nose: Wide nasal bridge 6. Mouth: Cleft lip/palate, bilateral cleft lip 7. GI: Hirschsprung disease occasionally (loss of ganglia from gut) 8. Neuro: Spina bifida, lumbosacral myelomeningocele Human brain development and subdivision by ‘vesicles’ Moore & Persaud 2003 Development along the radial axis in neurogenesis Neural stem cells Meninges derived from Semaphorins from meninges mesoderm and NC cells Figure 22-98 Molecular Biology of the Cell (© Garland Science 2008) Layering in the cortex and elsewhere reflects ‘birth’ order Figure 22-99 Molecular Biology of the Cell (© Garland Science 2008) Summary • Neurulation refers to the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube. The embryo at this stage is termed the neurula. • Begin the patterning of neural differentiation along the D-V, A-P and radial (proximo-distal) axes • Create and disseminate neural crest cells • Later, establish the important architectural features of the hindmid- and forebrain, with closure of the neural tube