Neurulation transforms the neural plate into the neural tube, forming the central nervous system. This process involves complex cell shape changes, signaling gradients, and precise closure mechanisms. Failed closure can lead to serious birth defects.

The notochord plays a crucial role in nervous system patterning. It secretes Sonic hedgehog, creating signaling gradients that establish distinct progenitor domains along the neural tube. These domains give rise to different types of neurons.

Neurulation and Neural Tube Formation

Neural Plate Formation and Folding

• Neurulation transforms neural plate into neural tube forming central nervous system precursor
• Neural plate induced by notochord signals along dorsal midline during gastrulation
• Neural plate folding driven by cell shape changes
  • Apical constriction causes cells to become wedge-shaped
  • Results in formation of neural groove
• Neural folds elevate and converge towards midline
  • Eventually fuse to form neural tube in primary neurulation

Neural Tube Closure and Defects

• Closure begins at multiple initiation sites
  • Proceeds in zipper-like fashion along embryo
• Anterior and posterior neuropores close last
• Secondary neurulation occurs in caudal region of some vertebrates
  • Neural tube forms through cavitation of solid cell cord
• Failed closure leads to neural tube defects
  • Anencephaly (brain and skull do not develop)
  • Spina bifida (incomplete closure of spinal cord)

Notochord Signaling in Nervous System Patterning

Notochord as Primary Organizer

• Rod-like mesodermal structure forms during gastrulation
• Serves as primary organizer for developing nervous system
• Secretes Sonic hedgehog (Shh) morphogen
  • Induces floor plate formation in ventral neural tube
• Floor plate becomes secondary signaling center
  • Also secretes Shh establishing ventral-to-dorsal gradient

Signaling Gradients and Neural Tube Patterning

• Bone Morphogenetic Proteins (BMPs) from dorsal ectoderm antagonize Shh
• Shh and BMP gradients create dorsal-ventral gene expression axis
• Establishes distinct progenitor domains along neural tube
  • Ventral domains give rise to motor neurons
  • Dorsal domains produce sensory neurons
• Notochord induces sclerotome formation in adjacent somites
  • Contributes to vertebral column development

Neural Crest Cell Formation and Differentiation

Neural Crest Induction and Migration

• Multipotent cell population arises at neural plate and non-neural ectoderm border
• Induction involves complex BMP, Wnt, and FGF signaling interplay
• Undergo epithelial-to-mesenchymal transition (EMT)
  • Delaminate from dorsal neural tube
  • Migrate extensively throughout embryo
• Migration guided by intrinsic factors and environmental cues
  • Chemotactic signals (CXCL12, semaphorins)
  • Extracellular matrix interactions (fibronectin, laminin)

Neural Crest Derivatives and Contributions

• Cranial neural crest forms craniofacial structures
  • Bones (maxilla, mandible)
  • Cartilage (nasal, ear)
  • Connective tissues of face and neck
• Trunk neural crest gives rise to various cell types
  • Melanocytes in skin
  • Schwann cells of peripheral nervous system
  • Sympathetic and parasympathetic ganglia
• Cardiac neural crest contributes to heart development
  • Forms outflow tract
  • Crucial for cardiac septation (dividing heart chambers)

Early Organogenesis and Primitive Gut Development

Primitive Gut Tube Formation

• Organogenesis begins fourth week of human embryonic development
• Primitive gut tube forms from endoderm
  • Initially straight tube divided into three regions
• Foregut develops into:
  • Pharynx, esophagus, stomach, proximal duodenum
  • Associated organs (liver, pancreas)
• Midgut forms:
  • Distal duodenum, jejunum, ileum
  • Cecum, appendix, ascending colon
  • Proximal two-thirds of transverse colon
• Hindgut gives rise to:
  • Distal one-third of transverse colon
  • Descending colon, sigmoid colon, rectum
  • Upper part of anal canal

Gut Tube Patterning and Organ Specification

• Differential growth rates cause gut tube folding
  • Forms specific organs
  • Positions organs within body cavity
• Reciprocal interactions crucial for proper development
  • Endoderm and surrounding mesoderm communicate
  • Guides organ specification (pancreatic buds, liver diverticulum)
• Molecular signaling pathways direct regional identity
  • Sonic hedgehog (Shh) patterns foregut
  • Fibroblast growth factors (FGFs) influence hindgut development