Developmental Neurobiology of the Vertebrate Brain
Inhoudsopgave
LECTURE 1, BRAIN DEVELOPMENT – RUUD TOONEN ....................................................................................... 2
PART 1: EARLY DEVELOPMENT OF THE MAMMALIAN BRAIN .............................................................................................. 2
PART 2: DEVELOPMENT OF CORTICAL LAYERS .............................................................................................................. 19
LECTURE 2, POLARITY– RUUD TOONEN ......................................................................................................... 28
PART 1. DEVELOPMENT OF NEURONAL POLARIZATION ................................................................................................... 28
PART 2. CYTOSKELETAL DYNAMICS & INTRACELLULAR TRANSPORT ................................................................................... 34
PART 3. EXTRACELLULAR CUES ................................................................................................................................. 41
PART 4. SIGNALLING PATHWAYS ................................................................................................................................ 45
PART 5. MAINTENANCE OF NEURONAL POLARITY AND AXONAL COMPARTMENTALIZATION .................................................... 47
LECTURE 3, HUMAN NEURONS – MARIEKE MEIJER........................................................................................ 52
WHY USE INDUCED PLURIPOTENT STEM CELLS TO STUDY NEURODEVELOPMENT .................................................................. 52
DIFFERENT APPROACHES TO INDUCE HUMAN NEURONS ................................................................................................. 54
OPTIMIZATION OF INDUCTION PROTOCOLS .................................................................................................................. 63
LECTURE 4, AXON GUIDANCE – RUUD TOONEN ............................................................................................. 71
HISTORY .............................................................................................................................................................. 71
FINDING GUIDANCE CUES ........................................................................................................................................ 74
OVERVIEW OF DIFFERENT GUIDANCE CUES .................................................................................................................. 78
Netrins ......................................................................................................................................................... 79
SLIT............................................................................................................................................................... 83
Ephrins ......................................................................................................................................................... 85
Semaphorins ................................................................................................................................................ 87
STEERING THE GROWTH CONE .................................................................................................................................. 88
LECTURE 5, SYNAPSE DEVELOPMENT – MARIEKE MEIJER .............................................................................. 94
INITIAL AXO-DENDRITIC CONTACT .............................................................................................................................. 95
- BIDIRECTIONAL NEURITE SPEED DATING .................................................................................................................... 97
ASSEMBLY OF SYNAPTIC COMPONENTS ..................................................................................................................... 102
CLUSTERING ....................................................................................................................................................... 105
MATURATION ..................................................................................................................................................... 106
- NEUREXIN-NEUROLIGIN IN SYNAPTOGENESIS (EXAM QUESTION?) ................................................................................ 107
MASTERCLASS, AIS DEVELOPMENT – AMELIE FREAL.................................................................................... 111
AIS FORMATION DURING EMBRYONIC DEVELOPMENT .................................................................................................. 113
ANKRYIN G ISOFORMS .......................................................................................................................................... 115
CROSS-TALK BETWEEN THE MEMBRANE COMPLEX AND CYTOSKELETON ........................................................................... 116
DOES THIS DYNAMIC INTERPLAY ALLOW FOR AIS REMODELING DURING PLASTICITY? .......................................................... 120
,Lecture 1, Brain Development – Ruud Toonen
The brain is who we are
- Einstein has more astrocytes in his brain than the average person
- Cogito, ergo sum – I think, therefore I am
Neurodevelopmental disorders (half of our brain disorders are neurodevelopmental)
- Quite common à 2-5% of all children
o depends if you count ADHD (on the border of being a developmental disorder)
- There are around 700 rare brain disorders, and these are all developmental disorders
- These children have this disease for their whole life
o Caregivers oKen need to take care of them for their whole life
o OKen they cannot talk or walk
- Shared molecular pathways
o Explains the fact of comorbidityà if you have mental retardaOon, you very
oKen also have epilepsy (lot of crosstalk)
o But these disorders are super complex
Part 1: Early development of the mammalian brain
- Neural tube to early brain
- Compartments
The development of the brain is super early during development
- The CNS and heart already develop in week 3 of the pregnancy
o At this Ome point, you oKen don’t even know you are pregnant yet
o One of the earliest events in embryogenesis
- This is quite conserved among species
o in the first days, you cannot disOnguish a chicken and a human
,Development of the human embryo
First week
- You go from 2 cell stage to 4 cell stage
- AKer a couple of days you have a blastula with blastula cells
- Blastocysts are cells forming the inner cells mass
o The inner mass are stem cells that will become the embryo
- In the old days when KO were made, blastocyst cells were used
o Embryonic stem cells that can get all cellular fates
- Blastocyst is a ball with fluid and cells
In the second week
- Looking from the top of the ball, a groove will develop called the primiOve streak
o From caudal to rostral
o The formaOon of this groove we call gastrulaOon: The ball is invaginaOng itself
In week 3 (looking from the top)
- The primiOve streak has somites and extends over the whole blastula
o We now call it a neurula
- You now already have cells with neuronal features
, GastrulaOon (week 3)
NeurulaOon is the developmental process during which the nervous system begins to form,
starOng from about three weeks of embryonic development. It follows gastrula8on, when
the embryo establishes its three germ layers — ectoderm, mesoderm, and endoderm —
and starts shaping into more complex structures.
From Gastrula8on to Neurula8on
• At three weeks, the primi8ve streak forms.
o This is the site where cells begin to migrate inward, marking the start of the
embryo’s body axis.
o The primiOve streak defines the area that will become the brain (cranial end)
and spinal cord (caudal end).
• The process begins from the blastula, a spherical mass of cells that
undergoes gastrula8on—an invaginaOon or inward folding that produces the three
germ layers:
o Endoderm: urinary, digesOve, and respiratory systems
o Ectoderm: Skin (epidermis), and nervous system
§ If you do nothing about ectoderm: skin cell fate
• You need to know which step is important to determine
neuronal fate
o Mesoderm: skeletal, muscular, and cardiovascular system
-
Inhoudsopgave
LECTURE 1, BRAIN DEVELOPMENT – RUUD TOONEN ....................................................................................... 2
PART 1: EARLY DEVELOPMENT OF THE MAMMALIAN BRAIN .............................................................................................. 2
PART 2: DEVELOPMENT OF CORTICAL LAYERS .............................................................................................................. 19
LECTURE 2, POLARITY– RUUD TOONEN ......................................................................................................... 28
PART 1. DEVELOPMENT OF NEURONAL POLARIZATION ................................................................................................... 28
PART 2. CYTOSKELETAL DYNAMICS & INTRACELLULAR TRANSPORT ................................................................................... 34
PART 3. EXTRACELLULAR CUES ................................................................................................................................. 41
PART 4. SIGNALLING PATHWAYS ................................................................................................................................ 45
PART 5. MAINTENANCE OF NEURONAL POLARITY AND AXONAL COMPARTMENTALIZATION .................................................... 47
LECTURE 3, HUMAN NEURONS – MARIEKE MEIJER........................................................................................ 52
WHY USE INDUCED PLURIPOTENT STEM CELLS TO STUDY NEURODEVELOPMENT .................................................................. 52
DIFFERENT APPROACHES TO INDUCE HUMAN NEURONS ................................................................................................. 54
OPTIMIZATION OF INDUCTION PROTOCOLS .................................................................................................................. 63
LECTURE 4, AXON GUIDANCE – RUUD TOONEN ............................................................................................. 71
HISTORY .............................................................................................................................................................. 71
FINDING GUIDANCE CUES ........................................................................................................................................ 74
OVERVIEW OF DIFFERENT GUIDANCE CUES .................................................................................................................. 78
Netrins ......................................................................................................................................................... 79
SLIT............................................................................................................................................................... 83
Ephrins ......................................................................................................................................................... 85
Semaphorins ................................................................................................................................................ 87
STEERING THE GROWTH CONE .................................................................................................................................. 88
LECTURE 5, SYNAPSE DEVELOPMENT – MARIEKE MEIJER .............................................................................. 94
INITIAL AXO-DENDRITIC CONTACT .............................................................................................................................. 95
- BIDIRECTIONAL NEURITE SPEED DATING .................................................................................................................... 97
ASSEMBLY OF SYNAPTIC COMPONENTS ..................................................................................................................... 102
CLUSTERING ....................................................................................................................................................... 105
MATURATION ..................................................................................................................................................... 106
- NEUREXIN-NEUROLIGIN IN SYNAPTOGENESIS (EXAM QUESTION?) ................................................................................ 107
MASTERCLASS, AIS DEVELOPMENT – AMELIE FREAL.................................................................................... 111
AIS FORMATION DURING EMBRYONIC DEVELOPMENT .................................................................................................. 113
ANKRYIN G ISOFORMS .......................................................................................................................................... 115
CROSS-TALK BETWEEN THE MEMBRANE COMPLEX AND CYTOSKELETON ........................................................................... 116
DOES THIS DYNAMIC INTERPLAY ALLOW FOR AIS REMODELING DURING PLASTICITY? .......................................................... 120
,Lecture 1, Brain Development – Ruud Toonen
The brain is who we are
- Einstein has more astrocytes in his brain than the average person
- Cogito, ergo sum – I think, therefore I am
Neurodevelopmental disorders (half of our brain disorders are neurodevelopmental)
- Quite common à 2-5% of all children
o depends if you count ADHD (on the border of being a developmental disorder)
- There are around 700 rare brain disorders, and these are all developmental disorders
- These children have this disease for their whole life
o Caregivers oKen need to take care of them for their whole life
o OKen they cannot talk or walk
- Shared molecular pathways
o Explains the fact of comorbidityà if you have mental retardaOon, you very
oKen also have epilepsy (lot of crosstalk)
o But these disorders are super complex
Part 1: Early development of the mammalian brain
- Neural tube to early brain
- Compartments
The development of the brain is super early during development
- The CNS and heart already develop in week 3 of the pregnancy
o At this Ome point, you oKen don’t even know you are pregnant yet
o One of the earliest events in embryogenesis
- This is quite conserved among species
o in the first days, you cannot disOnguish a chicken and a human
,Development of the human embryo
First week
- You go from 2 cell stage to 4 cell stage
- AKer a couple of days you have a blastula with blastula cells
- Blastocysts are cells forming the inner cells mass
o The inner mass are stem cells that will become the embryo
- In the old days when KO were made, blastocyst cells were used
o Embryonic stem cells that can get all cellular fates
- Blastocyst is a ball with fluid and cells
In the second week
- Looking from the top of the ball, a groove will develop called the primiOve streak
o From caudal to rostral
o The formaOon of this groove we call gastrulaOon: The ball is invaginaOng itself
In week 3 (looking from the top)
- The primiOve streak has somites and extends over the whole blastula
o We now call it a neurula
- You now already have cells with neuronal features
, GastrulaOon (week 3)
NeurulaOon is the developmental process during which the nervous system begins to form,
starOng from about three weeks of embryonic development. It follows gastrula8on, when
the embryo establishes its three germ layers — ectoderm, mesoderm, and endoderm —
and starts shaping into more complex structures.
From Gastrula8on to Neurula8on
• At three weeks, the primi8ve streak forms.
o This is the site where cells begin to migrate inward, marking the start of the
embryo’s body axis.
o The primiOve streak defines the area that will become the brain (cranial end)
and spinal cord (caudal end).
• The process begins from the blastula, a spherical mass of cells that
undergoes gastrula8on—an invaginaOon or inward folding that produces the three
germ layers:
o Endoderm: urinary, digesOve, and respiratory systems
o Ectoderm: Skin (epidermis), and nervous system
§ If you do nothing about ectoderm: skin cell fate
• You need to know which step is important to determine
neuronal fate
o Mesoderm: skeletal, muscular, and cardiovascular system
-
