molecular genetics and early embryonic development Flashcards
Paradigm of Development
In every species and at every level of
organization, complex structures are made
by repeating a few basic themes with
variations.
Stages of Embryonic Development
dif
growth
patterning
differentiation
cells begin to form specific and specialized structures.
growth
cell divisions that form more cells with identical functions as the parental cell.
patterning, deminsions?
cells produced by cleavage get organized into layers and groups of cell masses through what is known as gastrulation.
• Patterning needs to occur in 3 dimensions
– Anterior-Posterior (top-bottom)
– Dorsal-Ventral (left-right)
– Proximal-Distal (front-back)
Craniofacial Anomalies Account for? why?
1/3 all congenital defects
development occurs 3-8wks, most susceptible time for malformations
4 Important Concepts of Embryonic Development
- Universal Mechanisms of Animal Development
- Proteins can be substituted across species
- Inductive signaling
- Regional Determination
Universal Mechanisms of Animal Development
Multicellular animals are enriched in proteins mediating cell interactions and gene regulation
the 5 main signaling paths: RTK, TGFB, Wnt, Hedgehog, Notch
Hierarchical Gene Control diagram
protein substitution
- Multicellular organisms are enriched in proteins mediating cell interactions and gene regulation, could be different protein among species but sam role
- Regulatory DNA defines the development program=promoter region, etc.
Important Concepts of Embryonic Development: types of divisions? signaling?
- Asymmetric versus Symmetric Cell Division
* Inductive Signaling/ Morphogens
Asymmetric vs. Symmetric Division
both usually with equal distribution of DNA but the distribution of cytoplasmic contents may vary
Inductive Signaling, components?
could lead to?
- Starting Point (cell or cell cluster)
- Cell – cell signaling
- Cell signaling cascades
- Acts over great distances
produces a gradient of factors to cause the differentiation of nearby cells by altering gene expression, can lead to sequential induction
Sequential Induction
cells formed via inductive signaling may produce new signals that can then lead to the differentiation of new cell types
Morphogen Gradients
could be inducer or inhibitor gradient
Gastrulation simple definiton
Early developmental process in which the embryo (week 3 in humans) transforms from a single cell layer (blastula) into the three primary germ layers:
Early Embryonic Development/ formation of the primitive streak
primitive streak will form giving rise to hensons node; this will define the 3 planes of development (A-P, D-V, M-L)
cells will migrate in and form the various cell layers; endo, meso and ectoderm
(endo formed at hypoblast and ecto formed at exterior with the meso forming between these)
Regional Determination
cells will commit to certain cascades and form particular structures in different regions, can be transplanted but will still form the structure it was committed to
Craniofacial Syndromes
how many?
infant mortality?
howmman y births exhibit these?
- > 700 distinct syndromes
- Significant cause of infant mortality
- 3% of all live births exhibit some form of minor or major abnormality
Craniofacial Development events
- Neural tube development and closure
- Formation of ectoderm, somites, mesoderm and other cell masses
- Neural crest cell development, differentiation and migration
- Tissue-tissue interactions
- Tissue specific patterns of gene expression
- Reciprocal Induction
- Growth and mineralization of bones and teeth
- Neural development
- Muscle development
signals of the embryo directionality
cells may produce ventralizing, dorsalizing and lateralizing signals to form structures
Paraxial mesoderm development and differentiation pathway
Neural Crest Cells
origin?
stemness?
migration?
Embryonic cell population that is localized between the developing neural tube and the epidermis. (adult ones possible)
• Some neural crest cell exhibit “stemness” in that they can give rise to multiple differentiated cell types.
• In the formation of the craniofacial structures (and many other structures) the neural crest cells migrate through restricted pathways to form the developing structures.
• Cell migration is a tightly regulated process and the NCCs receive cues such as morphogens and growth factors that restrict their movement and determine fate.
Neural Crest Cells and the Skull, driven by what pathways?
skull formed from these cells (pharyngeal arches)
driven by the 5 major signaling pathways
Tooth Development basic
ectoderm and mesenchyme interact with one another, invagination into the mesenchyme and ecto produces cell signals to cause release of various factors that can then go back and forth between the two layers leading to tooth formation (GF, TF, etc.)
Genetics of Tooth Development (mutations)
number?
effects?
most common genetic diseases?
- Over 300 genes identified that have mutations associated with tooth patterning, morphogenesis defects and cell differentiation defects
- As a collective group craniofacial genetic diseases are the most common
Genetic Diseases of the Dentition
Ectodermal dysplasias Tooth Agenesis Supernumerary Teeth Cleft Lip/Palate (OMIM lists 565 entries) Skeletal Diseases
Types of Tooth Agenesis
- Hypodontia: common types of tooth agenesis with only a few missing teeth
- Oligodontia: more severe form of tooth agenesis with at least 6 missing teeth, excluding third molars
- Anodontia: complete lack of teeth
- Microdontia: one or more teeth appear smaller
- Macrodontia: one or more teeth grow faster and exceed average size
Key Signaling Pathways in Tooth Development, induced by?
involves the 5 major paths in which their activity is induced by the ecto/mesenchyme interactions
Ectodermal dysplasias
– >100 different disorders
– Commonly involves one or more of teeth, nails, skin, sweat glands
and/or hair
homeobox code and tooth formation
A homeobox code will drive the expression of singling factors for tooth formation and determine the class of tooth formed
period of greastest risk of dev abnomrlaities?
3-8 weeks, embryogenesis
