2022/2023 Molecular Principles
of Development
Lectures
Kevin Booij
RADBOUD UNIVERSITY
2022/2023
,Inhoud
Introduction - Molecular principles of development (07-11-2022) ........................................................ 2
Lecture 1 - Molecular principles of development (07-11-2022) ............................................................. 2
Lecture 2 - Molecular principles of development (08-11-2022) -MPD_Axes_Germ-layers_1 .............. 10
Lecture 3 – 21-11-2022 Molecular Principles of Development: Origin and specification of the germ
layers in vertebrates .............................................................................................................................. 16
Lecture 3 (part 2) – 21-11-2022 Molecular Principles of Development: Morphogenesis (overall
plaatjes nog bij doen vanuit de powerpoint!!!!!).................................................................................. 20
Lecture 4 – Anterior posterior patterning and organogenesis – Molecular principles of development-
Zhou ....................................................................................................................................................... 24
Lecture 5 (online lecture 6)– Antero-posterior pattering and Organogenesis – Zhou ......................... 32
Lecture 6 – Germ cells, fertilization and sex (chapter 9) Molecular principles of development .......... 42
Lecture 7 – (deel 8 op Brightspace) Fertilization and Sex – Hendrik Marks ......................................... 49
Lecture 8 – Cell differentiation 1 – Molecular principles of Development (06-12-2022) ..................... 54
,Introduction - Molecular principles of development (07-11-2022)
Molecular principles of development (6th edition) book is advised
• Zebrafish, frog and mice are model species
• In situ hybridization of zebrafish embryo’s during observation practical
• Q&A lectures (three sessions of 2 hours), prepare the questions, then discuss them during
the first hour and then the 2nd hour interactive lecture
• Computer practical – cirrus login
o 20% of final grade is the computer practical before Christmas
o Open questions, multiple choice and other
o Embryo development, recognize and identify the stages of embryonic development
▪ Development of regions and connection between expression patterns and
particular molecular processes at a certain stage
Lecture 1 - Molecular principles of development (07-11-2022)
____________________________________________________________________
Learning goals:
• Comparison of development in different species (Drosophila versus vertebrates)
• Drosophila development
o Syncytium, blastoderm
o Role of RNA transport, regulation of translation and protein diffusion
o Maternal, gap, pair-rule, segmentation and selector genes
• Forward genetics
• Vertebrate development: Blastula, gastrula, neurula
• Patterning, body axes (A-P, D-V)
• Germ layers (endoderm, mesoderm, ectoderm) and derivatives
• Fate, induction, determination, mosaic, regulative
• In situ hybridization for analysis of localized gene expression
Recommended study materials:
• Chapter 1, Chapter 2 (2.1-2.10), and chapter 3 (3.1-3.2), Wolpert et al, Principles of
Development (6th ed.)
• Lecture content (posted on Brightspace)
▪ Drosophila development
o Syncytium, blastoderm, imaginal disc
o Role of RNA transport, regulation of translation and protein diffusion
o Maternal, gap, pair-rule, segmentation and selector genes
▪ Forward genetics
▪ Drosophila versus vertebrate life cycle
▪ Blastula, gastrula, neurula
▪ Patterning, body axes (A-P, D-V)
▪ Germ layers (endoderm, mesoderm, ectoderm) for frog, fly and zebrafish
o Cleavage → Blastulation → Gastrulation → Neurolation?????
▪ Fate, induction, determination, mosaic, regulative
____________________________________________________________________
Drosophila (fly) used for illustrations of developmental concepts
, • Developmental biology
o Relations between disease, development and differentiation
▪ Congenital disease
▪ Cancer
▪ Aging
o Potential of regenerative medicine: applications of stem cells
▪ Disease modeling (iPS/ ES cell differentiation)
▪ Tissue engineering
• Forward genetics
o Make random mutations
o Limited number of times
o Look in the embryos to see the effects and identify phenotype to see which gene
expression causes that specific phenotypes.
• Reverse genetics
o Specifically knock out a gene to look at the effect or function of that specific gene
o Screen for genes expressions which are connected to the gene of interest
For drosophila:
• GAP genes
o Are expressed in various parts with gaps in between. Betere uitleg!
• Pair-rule genes
o .
• Segmentation genes
o .
These three genes are related to the segmentation of the body of flies
• Selector polarity genes
o .
o HOX genes
▪ Barcode for where you are in the embryo for each cell
▪ Genomic position
▪ Timing of expression
▪ Mutate them, they will cause homeotic mutations, if you mess with them,
the cells don’t know where they are. May result in an extra pair of wings.
▪ Homeotic genes (HOX genes)!!!
Drosophila (fly)
• Polarity in it, not all sides are the same in the egg of the drosophila
• Micropile, entry site for sperm in the cell of the drosophila
• Syncutium: many nuclei with shared cytoplasm (no cell membranes), allowing for diffusion of
proteins to pattern the embryo.
• This allows for free diffusion of proteins
• A blastoderm (germinal disc, blastodisc) is a single layer of embryonic epithelial tissue that
makes up the blastula.
, • The imaginal disks differentiate into most of the structures of the adult insect, such as the
legs, wings, and head.
▪ Not al details of Gastrulation and segmentation
o Tube for the nervous system In flies at the ventral side ( in humans on the back,
dorsal)????
▪ Cells are already interacted with segmentation before the actions are performed
of Development
Lectures
Kevin Booij
RADBOUD UNIVERSITY
2022/2023
,Inhoud
Introduction - Molecular principles of development (07-11-2022) ........................................................ 2
Lecture 1 - Molecular principles of development (07-11-2022) ............................................................. 2
Lecture 2 - Molecular principles of development (08-11-2022) -MPD_Axes_Germ-layers_1 .............. 10
Lecture 3 – 21-11-2022 Molecular Principles of Development: Origin and specification of the germ
layers in vertebrates .............................................................................................................................. 16
Lecture 3 (part 2) – 21-11-2022 Molecular Principles of Development: Morphogenesis (overall
plaatjes nog bij doen vanuit de powerpoint!!!!!).................................................................................. 20
Lecture 4 – Anterior posterior patterning and organogenesis – Molecular principles of development-
Zhou ....................................................................................................................................................... 24
Lecture 5 (online lecture 6)– Antero-posterior pattering and Organogenesis – Zhou ......................... 32
Lecture 6 – Germ cells, fertilization and sex (chapter 9) Molecular principles of development .......... 42
Lecture 7 – (deel 8 op Brightspace) Fertilization and Sex – Hendrik Marks ......................................... 49
Lecture 8 – Cell differentiation 1 – Molecular principles of Development (06-12-2022) ..................... 54
,Introduction - Molecular principles of development (07-11-2022)
Molecular principles of development (6th edition) book is advised
• Zebrafish, frog and mice are model species
• In situ hybridization of zebrafish embryo’s during observation practical
• Q&A lectures (three sessions of 2 hours), prepare the questions, then discuss them during
the first hour and then the 2nd hour interactive lecture
• Computer practical – cirrus login
o 20% of final grade is the computer practical before Christmas
o Open questions, multiple choice and other
o Embryo development, recognize and identify the stages of embryonic development
▪ Development of regions and connection between expression patterns and
particular molecular processes at a certain stage
Lecture 1 - Molecular principles of development (07-11-2022)
____________________________________________________________________
Learning goals:
• Comparison of development in different species (Drosophila versus vertebrates)
• Drosophila development
o Syncytium, blastoderm
o Role of RNA transport, regulation of translation and protein diffusion
o Maternal, gap, pair-rule, segmentation and selector genes
• Forward genetics
• Vertebrate development: Blastula, gastrula, neurula
• Patterning, body axes (A-P, D-V)
• Germ layers (endoderm, mesoderm, ectoderm) and derivatives
• Fate, induction, determination, mosaic, regulative
• In situ hybridization for analysis of localized gene expression
Recommended study materials:
• Chapter 1, Chapter 2 (2.1-2.10), and chapter 3 (3.1-3.2), Wolpert et al, Principles of
Development (6th ed.)
• Lecture content (posted on Brightspace)
▪ Drosophila development
o Syncytium, blastoderm, imaginal disc
o Role of RNA transport, regulation of translation and protein diffusion
o Maternal, gap, pair-rule, segmentation and selector genes
▪ Forward genetics
▪ Drosophila versus vertebrate life cycle
▪ Blastula, gastrula, neurula
▪ Patterning, body axes (A-P, D-V)
▪ Germ layers (endoderm, mesoderm, ectoderm) for frog, fly and zebrafish
o Cleavage → Blastulation → Gastrulation → Neurolation?????
▪ Fate, induction, determination, mosaic, regulative
____________________________________________________________________
Drosophila (fly) used for illustrations of developmental concepts
, • Developmental biology
o Relations between disease, development and differentiation
▪ Congenital disease
▪ Cancer
▪ Aging
o Potential of regenerative medicine: applications of stem cells
▪ Disease modeling (iPS/ ES cell differentiation)
▪ Tissue engineering
• Forward genetics
o Make random mutations
o Limited number of times
o Look in the embryos to see the effects and identify phenotype to see which gene
expression causes that specific phenotypes.
• Reverse genetics
o Specifically knock out a gene to look at the effect or function of that specific gene
o Screen for genes expressions which are connected to the gene of interest
For drosophila:
• GAP genes
o Are expressed in various parts with gaps in between. Betere uitleg!
• Pair-rule genes
o .
• Segmentation genes
o .
These three genes are related to the segmentation of the body of flies
• Selector polarity genes
o .
o HOX genes
▪ Barcode for where you are in the embryo for each cell
▪ Genomic position
▪ Timing of expression
▪ Mutate them, they will cause homeotic mutations, if you mess with them,
the cells don’t know where they are. May result in an extra pair of wings.
▪ Homeotic genes (HOX genes)!!!
Drosophila (fly)
• Polarity in it, not all sides are the same in the egg of the drosophila
• Micropile, entry site for sperm in the cell of the drosophila
• Syncutium: many nuclei with shared cytoplasm (no cell membranes), allowing for diffusion of
proteins to pattern the embryo.
• This allows for free diffusion of proteins
• A blastoderm (germinal disc, blastodisc) is a single layer of embryonic epithelial tissue that
makes up the blastula.
, • The imaginal disks differentiate into most of the structures of the adult insect, such as the
legs, wings, and head.
▪ Not al details of Gastrulation and segmentation
o Tube for the nervous system In flies at the ventral side ( in humans on the back,
dorsal)????
▪ Cells are already interacted with segmentation before the actions are performed
