PHYSL 371 - Gliogenesis, Neurogenesis, Organoids

lectures from Dr. Munz

What is gliogenesis? neurogenesis?

Gliogenesis is the development and formation of glial cells, and neurogenesis is the development and formation of neuronal cells

Important concepts regarding development/cell types:

1. Development moves in one direction

2. As a cell’s cell type develops, it’s potency decreases

3. Cell types are differentiated by gene expression → cell types develop through a change in transcription

4. Adult cell type identity is the result o fa gene regulatory network that determines gene expression

What are cell types?

transcriptionally similar cells

How is gene expression measured?

single cell transcriptomics → technology identifies gene expression/RNA in a single cell to determine cell type

How is gene expression determined to make different cell types?

Gene regulatory network is instructed by cellular environmental signals/cues → certain transcription factors are engaged and act on different promotors/enhancers, so the cell “reacts” to the signals

What is cell proliferation?

process where a cell grows, divides, and produces two identical daughter cells, leading to an exponential increase in cell numbers (grow, divide, grow, divide, grow, divide, etc.)

What is cell differentiation?

process by which unspecialized stem cells mature into specialized cells with distinct structures and functions (eg. nerve cells, muscle cells)

What is morphogenesis?

the biological process that causes a cell, tissue, or organism to develop its shape

What is programmed cell death?

process by which cells dies, usually to benefit an organism

What is dorsoventral patterning?

Embryonic cells assume different developmental fates (eventual cell types) based on their orientation on dorsoventral axis (dorsal = backside, ventral = belly side; but in the brain, dorsal = “up”, ventral = “down” because of how human necks bend)

Outline early morphogenesis

1. cells divide in fertilized egg, becomes blastocyst (50-150 cells) on day 5-6; some cells form an inner cell mass that will layer become embryo

2. blastocyst implants to uterine wall day 6

3. blastocyst separates into layers, embryo is flat disc with layers: ectoderm, mesoderm, endoderm 3 weeks

What do the early embryonic layers develop into?

Ectoderm - outer layer of skin, hair, nails, entire nervous system (brain, spinal cord, nerves)

Mesoderm - musculoskeletal system (bones, muscles, connective tissues), circulatory system, heart, kidneys, internal sex organs

Endoderm - linings of GI tract and respiratory system, organs (liver, pancreas, lungs, thyroid, bladder)

Outline neuronal induction in early morphogensis

1. ectoderm differentiates to form flat ribbon-like neural plate day 16

2. neural plate edges lift up to form neural folds, while the enters dips down to form neural groove

3. neural folds move toward embryo midline and fuse, turning the groove into hollow neural tube

4. anterior and posterior neuropores (ends of tube) close last day 25 anterior and day 28 posterior

   • during tube closure, come cells at the junction of the neural plate and epidermis migrate away as neural crest cells which become precursors for cell types like peripheral nerves and other tissues

5. neural tube develops into CNS, anterior end becoming brain and posterior end becoming spinal cord

Dorsoventral patterning is signaled by?

BMP (bone morphogenetic protein) on the dorsal side (roofplate) and SHH (sonic hedgehog 💀) on the ventral side (floorplate)

What is paracrine signaling?

local cellular communication where a cell releases signaling molecules (ligands) that diffuse a short distance through extracellular space to bind to/activate target cells in the immediate vicinity (Eg. BMP and SHH patterning the dorsoventral axis)

What is juxtracrine signaling?

direct form of cell-to-cell communication in multicellular organisms where a ligand on one cell surface interacts with a receptor on an adjacent cell (Eg. Notch-Delta signaling balancing neuron and glial cell differentiation)