Embryology An Introduction to Molecular Regulation and Signaling
Ass. Prof. Dr. Malak A. Al-yawerEmbryology
Why we study Embryology
B. The vast majority of physicians will have an opportunity to interact with women of childbearing age
Scientific approaches
to study embryology have progressed over hundreds of years
Scientific approaches
Anatomical approaches Experimental embryology Grafting experiments Molecular approaches
Anatomical approaches dominated early investigations
Optical equipment and dissection techniques.
Comparative and evolutionary studies to understand the progression of developmental phenomena to investigate offspring with birth defects, and compare to organisms with normal developmental patterns.
Experimental embryology
Trace cells during development to determine their cell lineages. Vital dyes were used to stain living cells to follow their fates. Radioactive labels and autoradiographic techniques Genetic markers
Grafting experiments
provided the first insights into signaling between tissues. Examples of such experiments included grafting the primitive node from its normal position on the body axis to another and showing that this structure could induce a second body axis.
Molecular approaches
Numerous means of identifying cells using Reporter genes, Fluorescent probes, and other marking techniques have improved our ability to map cell fates.
knockout, knock-in, and antisense technologies, has created new ways to produce abnormal development and allowed the study of a single genes function in specific tissues.
Molecular biology
Molecular biology has opened the doors
to new ways to study embryology and to enhance our understanding of normal and abnormal development.
Molecular biology
There are approximately 35,000 genes in the human genome, but these genes code for approximately 100,000 proteins. Genes are contained in a complex of DNA and proteins called chromatin.
Drawing showing nucleosomes that form the basic unit of chromatin.
Each nucleosome consists of an octamer of histone proteins and approximately 140 base pairs of DNA. Nucleosomes are joined into clusters by linker DNA and other histone proteins.
Chromatin
Heterochromatin In inactive state, chromatin appears as beads of nucleosomes on a string of DNA. Nucleosomes keep the DNA tightly coiled, such that it cannot be transcribed.
Euchromatin It is the uncoiled state . DNA must be uncoiled from the beads for transcription to occur
Induction and Organ Formation
Induction- Epithelial mesenchymal interactions
Cell Signaling
Cell-to-cell signaling is essential for induction and for cross talk between inducing and responding cells.
2 ) juxtacrine interactions, which do not involve diffusable proteins. Juxtacrine factors may include products of the extracellular matrix, ligands bound to a cells surface, and direct cell-to-cell communications
Signal transduction pathways
include a signaling molecule (the ligand) and a receptor. The receptor usually spans the cell membrane and is activated by binding with its specific ligand.
Mitosis
Mitosis
Is the process whereby one cell divides giving rise to two daughter cells that are genetically identical to the parent cell . Each daughter cell receives the complete complement of 46 chromosomes . Mitosis occurs in most somatic cells
The main stages of the mitotic cycle of a somatic cell
Interphase (replication phase)
Before a cell enters mitosis, each chromosome replicates its deoxyribonucleic acid (DNA).
The chromosomes are extremely long, they are spread diffusely through the nucleus, and they cannot be recognized with the light microscope.
Prophase
Prometaphase
only at prometaphase do the chromatids become distinguishable
Metaphase
Chromosomes line up in the equatorial plane and become attached to microtubules that are extending from centomeres to centrioles forming the mitotic spindle
Anaphase
The centromere of each chromosome divides, marking the beginning of anaphase, followed by migration of chromatids to opposite poles of the spindle.
Telophase
chromosomes uncoil and lengthen, the nuclear envelope reforms, and the cytoplasm divides
Each daughter cell receives half of all doubled chromosome material and thus maintains the same number of chromosomes as the mother cell.
Meiosis
Meiosis
Stages in the meiotic cycle
Meiosis I
Interphase cell
diploid ( 2 n ) chromosomes , tetraploid amount of DNA
prophase I ( 5 stages )
1. leptotene chromosomes initially thin then begin to shorten and thicken 2. zygotene homologus chromosomes begin to pair point for point . pachytene pairing is complete ,chromosomes still shortening
prophase I ( 5 stages )
4. diplotene chromatids and chiasmata now appear 5. diakinesis centromeres separate further , adhesion of exchanged segments
Characteristic events during meiosis I
Meiosis II
similar to mitosis the cross over and non cross chromatids separate randomly At the end of meiosis II , 4 daughter cells chromosome number remaining haploid , DNA is reduced to the haploid amount
Results of meiotic divisions
1. Genetic variability is enhanced through Cross over which creates new chromosomes Random distribution of homologus chromosomesb to daughter cells
2. each germ cell contains a haploid number of chromosomes so that at fertilization the diploid number of 46 is restored
A. The primitive female germ cell (primary oocyte) produces only one mature gamete, the mature oocyte. B. The primitive male germ cell (primary spermatocyte) produces four spermatids, all of which develop into spermatozoa.
Clinical correlations
1. chromosomal abnormalities A. numerical ( nondisjunction , translocation ) B. structural 2. gene mutations
Meiotic nondisjunction
During meiosis ,homologous chromosomes normally pair and then separate .if separation fails ( nondisjunction )
Non disjunction may involve 1. autosomes ( trisomy 21 , trisomy 13 , trisomy 18 ) 2. sex chromosomes Klinefelter syndrome (XXY ) 47 chromosomes , XXXY 48 chromosomes ) Turner syndrome (XO )
Normal maturation divisions. B. Nondisjunction in the first meiotic division. C. Nondisjunction in the second meiotic division.
Mitotic nondisjunction
Nondisjunction may occur during mitosis in an embryonic cell during earliest cell divisions . Such conditions produce mosaicism . Some cells having an abnormal chromosome number and others being normal )
Translocation
Structural abnormalities Results from chromosomal breakage
Partial deletion of a chromosome e.g. partial deletion of the short arm of chromosome 5 ( Cri-du-chat syndrome )
Microdeletions spanning only a few contiguous genes may result in microdeletion syndrome or contiguous gene syndrome. e.g. microdeletion on the long arm of chromosome 15
Thank you
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