Lecture 13: Early Brain Development Flashcards
What is gastrulation? When does it occur?
- Establishment of basic body axes
- Development of 3 embryonic germ cell layers from blastocyst
- Very soon after conception
What are the basic body axes?
Anterior-Posterior, Dorsal-Ventral, Medial-Lateral
What are the 3 embryonic germ cell layers?
- Ectoderm
- Mesoderm
- Endoderm
- Gives rise to specific sets of tissues or organs in the body
- Named for their relative position
Describe the ectoderm?
- Outer layer of tissue
- E.g. nervous system, skin
Describe the mesoderm?
- Middle layer of tissue
- E.g. blood vessels, kidneys
- Initiates the invagination that defines gastrulation
- Fold becomes neural tube
Describe the endoderm?
- Inner layer of tissue
- E.g. lining of lungs, liver
Where is the notochord formed?
- Midline of the gastrulating embryo
What is the notochord?
- Cylinder of mesodermal cells generated at the site of the surface indentation (primitive pit) that eventually elongates (primitive streak)
- This is the start of invagination
What does the notochord define?
- Embryonic midline and axis of symmetry for the body
Is the notochord permanent?
- No, it is transient
- Disappears following early development
Where does the notochord send inductive signals to? What is the result?
- Overlaying ectoderm
- Starts formation of nervous system
What is the neuroectoderm and what does it do?
- Ectoderm immediately dorsal to notochord
- Gives rise to entire nervous system
What leads to differentiation of cells into neuroectodermal precursor cells?
- Inductive signals from notochord trigger neuroectoderm
What forms the neural plate?
- Neuroectodermal precursor cells thicken into neural plate
What happens in neurulation?
- Lateral margins of neural plate (alar plate) fold inward
- Neural plate becomes neural groove that become neural tube
Is the neural tube homogenous?
- No
What are 2 main structures of neural tube?
- Floorplate
- Neural crest
Describe the floorplate?
- Cells at ventral portion form floorplate
- Specialized strip of epithelial-like cells
- Provide inductive signals for neuroectodermal precursors of spinal cord and hindbrain
Describe the neural crest?
- Emerges at lateral margins of neural plate
- ‘tips’
How do you know the neural tube is complete?
- Edges of neural plate meet at midline, then neural tube is complete
What does the neural crest become?
- Sensory and autonomic ganglia
- Peripheral nervous system
What does the mesoderm adjacent to the neural tube become?
- Thickens and subdivides into somites (precursors of skeleton and muscle)
What does the neural tube adjacent to somites become?
- Rudimentary spinal cord
What does the fluid-filled cavity of the neural tube become?
- The ventricular system
What happens to the anterior ends of the neural plate?
- AKA anterior neural folds
- Grow together at midline
- Continue to expand
- Eventually gives rise to brain
What do stem cells of the neural tube ultimately give rise to?
- Entire brain
- Spinal cord
- Much of PNS
What do floorplate and roofplate signal?
- Stem cell differentiation of spinal cord/hidbrain development from neural tube
What does the neural crest give rise to?
- Neurons and glia of sensory and autonomic ganglia
- And other non-neuronal structures
How many migratory paths do neural crest cells have?
- 4
What do the different migratory paths of neural crest cells allow for?
- Distinct cellular environment interactions
What are the migratory paths that neural crest cells have?
- Sensory ganglia
- Visceral motor (autonomic) ganglia
- Adrenal neurosecretory precursor cells aggregate around dorsal kidney
- Non-neuronal pigment, cartilage, bone (primarily of face/skull)
What happens after the formation of the neural tube?
- Major brain regions gradually begin to become apparent as differential growth causes bends/folds/constrictions of tube
What does the anterior end of the neural tube form?
- A crook
- Cephalic flexure
What does the cephalic flexure form?
- Balloons out
- Forms prosencephalon
- Gives rise to forebrain/cortex
What is the bulge that forms rostral to cephalic flexure and posterior to prosencephalon?
- Mesencephalon
- Gives rise to midbrain (substantia nigra and ventral tegmental area)
Where does the rhombencephalon form?
- Between cephalic flexure and caudal cervical flexure
- Gives rise to hindbrain
What does the neural tube caudal to the cervical flexure form?
- Spinal cord
What is the telencephalon? What aspects of the brain does it form?
- Lateral aspects of prosencephalon
- Most rostral part
- Cerebral cortex, hippocampus, basal ganglia, basal forebrain, olfactory bulb
What is the diencephalon and what does it form?
- Caudal portion of prosencephalon
- Thalamus, hypothalamus, optic vesicles (neural retina)
- Sensory processing
What is the mesencephalon and what does it consist of?
- Superior/inferior colliculi, midbrain tegmentum (including substantia nigra)
What is the metencephalon and what does it form?
- Rostral rhombencephalon
- Cerebellum, pons (of hindbrain)
What is the myencephalon and what does it become?
- Caudal rhombencephalon
- Medulla
What are neuromeres?
- Neural tube is organized into repeating units called neuromeres
What does the formation of neuromeres lead to?
- Segmentation
- Establish regional identity in body and possibly also brain
What are Hox genes responsible for?
- In hindbrain and spinal cord
- Guide differentiation of embryo into distinct segments
What are DLX and PAX genes and what are they responsible for?
- In midbrain and forebrain
- Guide differentiation of embryo into distinct segments
How many clusters of homologous genes for differentiation do flies have?
- One (on one chromosome)
How many clusters of homologous genes for differentiation do humans/other vertebrates have?
- 4
What does the pattern of Hox, DLX and PAX gene expression relate to?
- Formation of morphological features (shapes/bends/folds) that underlie progressive regionalization of developing neural tube
What is neural induction?
- Instructions that establish stem cell capacity to make nerve cells specific to each region
- Produce molecular signals that induce cell/tissue differentiation in vertebrate embryo
What happens when sections of developing embryo are cut out and transplanted to a different region?
- Acquired a new identity (influenced by local factors)
OR - Retained original identity (influenced by original, immutable instructions)
How can interactions b/n cells influence cell fate?
- Points of communication
- Local diffusible factors
- Direct physical interactions b/n membrane proteins
Which structures produce molecular signals that induce cell/tissue differentiation?
- Embryonic notochord
- Floorplate
- Neural ectoderm
- Somites
What are some results of inductive signalling?
- Change in gene expression, shape, and motility of target cells
What begins after the initial patterning of the neural tube is complete?
- Neurogenesis
What provides basic identities of precursor cells?
- Distinct signatures of gene expression
Where are precursor cells located?
- Ventricular zone
- Innermost cell layer surrounding lumen of neural tube (encapsulates ventricle)
What type of cell movements do precursor cells undergo? What does that lead to?
- Stereotyped pattern of cell movements
- Formation of new stem/precursor cells or neuroblasts (immature nerve cells)
Where is the nucleus located at the G1 growth stage?
- Cell body/nucleus is near ventricular surface
Where is the nucleus during the S/DNA synthesis stage?
- Nucleus migrates toward plial (outside) surface, DNA replicates
What happens during the G2 growth stage?
- Cell grows
- Nucleus migrates toward lumenal (ventricular) surface, precursor cell loses connection to outer surface (localized to ventricular surface)
What are the 2 ways that neural precursor cells can divide in mitosis?
Symmetrical -> two neural stem cells
Asymmetrical -> postmitotic neuroblast and another progenitor cell (daughter/stem cell) that reenters cell growth cycle
The notochord forms which germ layer?
- Mesoderm
The hypothalamus arises from which primitive brain region?
- Diencephalon
What is the main excitatory neurotransmitter in the adult brain?
- Glutamate
The primary transmitter released by the medium spiny neurons of the striatum is…
- GABA
Most neuroblasts that migrate long distances in CNS use what to guide them?
- Radial glial cells
- These are progenitor cells that can become neuronal progenitor cells, oligodendrocytes, and astrocytes
Where do postmitotic neurons move past? How?
- ## Postmitotic neurons adhere to glial process to move beyond dividing cells in ventricular and subventricular zones and past already-differentiating neurons in lower cortical layers of brian structures that express layered structure
What is gastrulation?
- Days 13-19
- Movement of cells toward midline then forward along midline forming primitive streak
What is the end result of gastrulation?
- Formation of ectoderm, endoderm and mesoderm
As ectoderm thickens, what does it become?
- Neural plate
What does the fluid filled inside of the neural tube become?
- Cerebral ventricles
- Central canal
- Connections between
How long does it take for prosencephalon, mesencephalon and rhombencephalon to become distinct?
- 24 days
What are the stages of neural development?
- Neurogenesis
- Neural migration
- Differentiation
- Process outgrowth
- Synaptogenesis
