2.Neurogenesis

What are the 4 kinds of typical model systems?

• C. Elegans (302 neurons)

• Drosophila (100k neurons)

• Frog (16 million neurons)

• Mouse and rat (75 and 56 million neurons, respectively)

What are the 3 layers of a germ plate?

• ectoderm (outer layer)

• mesoderm (middle layer)

• endoderm (inner layer)

Endoderm germ layer gives rise to…

• primitive gut

  • lung!

  • liver, pancreas, digestive tubes

• yolk sac

Mesoderm germ layer gives rise to…

• axial

• paraaxial

  • sclerotome → skeleton

  • myotome → skeletal muscles

• intermediate

• lateral

  • visceral mesoderm → heart, blood vessels

• head

Ectoderm germ layer gives rise to the ….

• epidermis → skin

• neural tubes → brain, spinal cord

Central Nervous System (CNS) arises from specialized epithelium—the neural plate. This process relies on the inhibition of ___ signaling?

Bone Morphogenetic Protein (BMP)

Neural crest cells derive from the dorsal neural tube and migrate out to form the ___ and melanocytes and cartilage in the head.

Neural crest cells have been shown to form at an intermediate level of BMP signaling.

Peripheral Nervous System (PNS)

What are the 3 early embryonic brain ventricles?

• Forebrain

• Midbrain

• Hindbrain

When developed, what are the 4 brain ventricles?

• first and second lateral ventricles

  • one in each cerebral hemisphere

• interventricular foramen

• third ventricle

  • one in diencephalon

• cerebral aqueduct

• fourth ventricle

  • one in hindbrain (pons and medulla)

• central canal

About Neural induction, most work was performed in amphibian embryos and the key molecule is BMP. What is neural induction?

process by which embryonic cells in the ectoderm make a decision to acquire a neural fate (to form the neural plate) rather than give rise to other structures such as epidermis or mesoderm

What is the default model for neural induction?

• BMPs are expressed in ectoderm on embryo’s ventral side, inducing ectoderm to become epidermis

• organizer on dorsal side releases inhibitors of BMPs like noggin, chordin, follistatin, which diffuse into ectoderm on dorsal side, block the effects of BMPs, and allow neural tissue to form

What is a Bone Morphogenetic Protein (BMP)?

• a member of the TGF-Beta (Transforming Growth Factors) family

• binding to their receptors (BMPR) activates the Smad pathway (transcription factor)

• inhibition of BMP (by inhibitors like noggin, chordin) induces neural differentiation

What is the default mode hypothesis?

Ectodermal cells will become neural type at neutral condition (in the absence of BMP)

All neurons and glia in the brain come from neural tube. Meanwhile, the number of cells is regulated at several levels:

1. by intrinsic limits of the number of progenitor cell division (ex: always 302 neurons in adult C. elegans)

2. by extracellular signals (mitogen and mitogen inhibitors)

3. by rate of cell death (programmed cell death = apoptosis)

Cell Cycle

• cytokinesis

• interphase (below are subphases)

  • G1

    • cellular contents, not chromosomes, are DUPLICATED

  • S

    • each of 46 chromosomes are DUPLICATED by cell

    • During S phase, all of the DNA in a cell is replicated, thereby doubling the amount of DNA in the cell

  • G2

    • cell “double checks” duplicated chromosomes for error, making any needed repairs

• Mitosis

  • division of one nucleus into two genetically-identical daughter nuclei (ex: mitosis of a somatic cell nucleus containing four chromosomes will produce two daughter nuclei containing four chromosomes each)

  • 1st phase: prophase

    • During prophase, chromatin in the cell's nucleus becomes condensed into discrete chromosomes

• also

  • G1 → G1 goes to cell cycle arrest aka STOPS

  • During interphase, the cell’s genetic content, or DNA, is dispersed within the nucleus as chromatin

During development,…

1. length of the cell cycle increases

2. increase is mainly at G1 phase

by the end of neurogenesis, nearly all cells leave the cell cycle and very few remain to generate new neurons (remember, neurons are postmitotic cells)

Neuron birthdating

• technique used to determine when neurons were born

• The developmental age at which a neuronal precursor cell exits the cell cycle

• reliable method for classifying neurons in different nervous systems

• early progenitor cell generates two distinct daughter cells after a mitotic division. This event is referred to as the neuronal birthdate of the daughter cell that is committed to a neuronal fate