EMBRYOLOGY AND GENETICS.pptx details for nurses

EMBRYOLOGY AND GENETICS

1. GENETICS

2. Learning objectives To briefly review the various terminologies used in genetics To list the symbols used in pedigree charts To mention the principles of inheritance To describe the human chromosome To describe the various types of genetic diseases especially chromosomal disorders

3. INTRODUCTION

4. Branch of science Deals with how we inherit physical and behavioral characteristics, including medical conditions

5. Genetics is the study of genes What is a gene? A. A factor that controls a heritable characteristic B. Something on a chromosome C. Information stored in a segment of DNA D. Something that encodes a protein

6. Recent discoveries impinge not just on rare genetic diseases and syndromes, but also on many of the common 'acquired' disorders of adult life that may be predisposed by genetic variation, s/a cardiovascular disease, psychiatric illness and cancer Consequently genetics is now widely accepted as being at the forefront of medical science

7. Importance of Genetics

8. Before moving on to our topics, it is worth a brief diversion to consider the merits of this unlikely creature, which has proved to be of great value in genetic research. The fruit fly, Drosophila , possesses several distinct advantages for the study of genetics: 1. It can be bred easily in a laboratory 2. It reproduces rapidly and prolifically at a rate of 20 to 25 generations per annum 3. It has a number of easily recognized characteristics, s/a curly wings and, a yellow body , that follow Mendelian inheritance 4. Drosophila melanogaster , the species studied most frequently, has only four pairs of chromosomes, each of which has a distinct appearance so that they can be identified easily 5. The chromosomes in the salivary glands of Drosophila larvae are among the largest known in nature, being at least 100 times bigger than those in other body cells

9. SOME COMMON TERMINOLOGIES

10. Deoxyribonucleic acid (DNA) The hereditary material Fundamental building block of life – coiled to form chromosomes Proteins called histones support DNA molecule within chromosome

11. Structure and composition DNA molecule consists of 2 linear chains twisted into shape of a double helix - nucleus (‘control centre’) of our cells Composed of a long polymers of nucleotides (Nitrogenous base, sugar- deoxyribose , phosphate group)

12. DNA-Structure In 1953 Watson and Crick – double helical structure of DNA with the help of X-ray crystallography, which was the work of Maurice Wilkins and Rosalind Franklin at King's College, London Watson and Crick suggested that the DNA molecule is composed of two chains of nucleotides arranged in a double helix The backbone of each chain is formed by phosphodiester bonds between the 3' and 5' carbons of adjacent sugars, the two chains being held together by hydrogen bonds between the nitrogenous bases, which point in towards the center of the helix

13. Every cell in our body has the same DNA

14. DNA.. The site where genes work is the cell. Each cell’s function within an organism is determined by the genetic information encoded in DNA.

15. The packaging of DNA into chromosomes involves several orders of DNA coiling and folding In addition to the primary coiling of the DNA double helix, there is secondary coiling around spherical histone 'beads', forming what are called nucleosomes There is a tertiary coiling of the nucleosomes to form the chromatin fibers that form long loops on a scaffold of non- histone acidic proteins, which are further wound in a tight coil to make up the chromosome as visualized under the light microscope, the whole structure making up the so-called solenoid model of chromosome structure

16. Gene Gene – region of DNA which codes for a specific protein Around 25,000 genes All of genes in cell (in nucleus and mitochondria) make up the genome

17. Genes contain instructions to make a particular protein Proteins are complex chemicals that are building blocks of our body

18. Additional terminologies.. Locus Every chromosome in a cell contains many genes, and each gene is located at a particular site (called locus ) on the chromosome Plural - Loci

19. Additional terminologies.. Allele One of the alternative forms of a gene Our cells have 2 alleles for each gene, one from each parent

20. Additional terminologies.. Genotype Genetic constitution or makeup of an individual Phenotype Appearance of an individual (physical, mental or biochemical) Results from an interaction of environment and genotype

21. Additional terminologies.. Homozygous : Individual inherited same alleles from each parent Heterozygous : Individual inherited different alleles from each parent

22. If both alleles of a diploid organism are the same , the organism is homozygous at that locus If they are  different , the organism is  heterozygous  at that locus If one allele is missing , it is  hemizygous Males are  hemizygous  for most genes on sex chromosomes, having only one X and one Y chromosome

23. Additional terminologies.. If only one copy of allele is required for expression of a character it is dominant If both copies of allele are required for expression of a character it is recessive

24. RNA A nucleic acid Single stranded Uracil replaces thymine

25. Additional terminologies.. Method for determing genotype in offspring involves construction of what is known as a Punnett's square

26. PEDIGREE CHARTING

27. A diagram to show the family relationships and mode of inheritance of a particular disorder Uses standardized set of symbols to represent people and lines to represent genetic relationships

28. Results in presentation of family information in the form of an easily readable chart

29. LAWS OF INHERITANCE

30. Gregor Mendel (1822-1884 AD) Our present understanding of human genetics owes much to work of Austrian monk Gregor Mendel Cross bred pea plants with different characteristics Observations led to laws regarding transmission of hereditary characteristics from generation to generation

31. Mendel studied contrasting characters in garden pea First filial or F1 generation – characteristics manifested were dominant F2 generation – characteristics that reappeared were recessive

32. Mendel's proposal was that plant characteristics being studied were each controlled by a pair of factors, one of which was inherited from each parent The pure-bred plants, with two identical genes, used in the initial cross would now be referred to as homozygous The hybrid F1 plants, each of which has one gene for tallness and one for shortness, would be referred to as heterozygous The genes responsible for these contrasting characteristics are referred to as allelomorphs , or alleles for short

33. Laws of Inheritance On the basis of Mendel’s pea plant ( Pisum sativum ) experiments Applicable to all animal species including human beings They are: 1] Law of Uniformity 2] Law of Segregation 3] Law of Independent Assortment

34. 1] Law of Uniformity Refers to the fact that when 2 homozygotes with different alleles are crossed, all offspring in F1 generation are identical and heterozygous In other words, characteristics do not blend , as had been believed previously, and can reappear in later generation

35. 2] Law of Segregation Each individual possess two genes for a particular characteristic and Only one of these genes can be transmitted at any one time

36. 3] Law of Independent Assortment Refers to the fact that members of different gene pairs segregate to offspring independently of one another

37. Chromosomal basis of inheritance As interest in Mendelian inheritance grew, there was much speculation as to how it actually occurred Subsequent studies by various scientists concluded that chromosomes could be the bearers of heredity and connection between Mendelian inheritance and chromosomes was made

38. CHROMOSOMES

39. Present in nucleus Chromo =color, soma =body Bearers of heredity DNA is coiled around histone protein to form a chromosome

40. Chromatin Chromosome in uncoiled state Interphase (resting phase) Chromosome Condensed chromatin network, at the time of cell division

41. Parts Chromatids One of the two identical parts of chromosome Centromere Point/constriction where 2 chromatids attach Divides chromosome into short (p) and long (q) arms Telomere Tip/free end of each chromosome arm Play a crucial role in sealing ends of chromosomes and maintaining structural integrity

42. Parts of a chromosome Centromere or kinetocore q segment (long arm) p segment (short arm) Telomere Satellite bodies

43. Chromosome number 46 (23 pairs) chromosomes except … 2 sex chromosomes : X and Y (46,XX; 46,XY) 44 chromosomes - autosomes

44. Classification 4 types (based on position of centromere ): Centrom -ere at end Centromere severely offset from center Centromere slightly offset from center Centromere in the center

45. Classification of chromosomes

46. Classification of human chromosome: Denver system Group A : long metacentric : 1,2 & 3 Group B : long submetacentric : 4 & 5 Group C : medium size submetacentric : 6 to 12 & X Group D : medium size acrocentric with satellite bodies: 13 to 15 Group E : short submetacentric : 16 to 18 Group F : short metacentric : 19 & 20 Group G : short acrocentric with satellite bodies: 21, 22 & Y

47. The study of chromosomes and cell division is referred to as cytogenetics

48. Karyotype A photomicrograph of an individual’s chromosomes, arranged in a standard manner ( descending order of height ) Indicated to detect chromosomal anomalies (both structural and numerical)

49. X-chromosome inactivation During interphase of cell cycle, inside the nuclei of somatic cells of female, one of the X chromosome is heterochromatic and inactive The inactive X chromosome exists in a condensed form during interphase when it appears as a darkly staining mass of chromatin known as the sex chromatin, or Barr body

50. Significance of Barr bodies Number of Barr body is 1 less than number of X chromosome Thus, counting number of Barr bodies can find out numerical anomalies of sex chromosomes Eg . Normal female (XX; 1 Barr body) Turner syndrome (XO; 0 Barr body) Klinefelter syndrome (47 XXY; 1 Barr body)

51. Mutation Defined as a heritable alteration or change in genetic material Permanent change in DNA Changes protein product of a gene Contribute to or cause a disease Vast majority occur spontaneously (errors in DNA replication and repair) and other arise through exposure to mutagenic agents s/a : Radiation (Ionizing ratiation , UV) Chemicals (Formaldehyde, Vinyl chloride)

52. Mutation Somatic cell mutation - Not transmitted to progeny but are important in causation of cancers Mutation in gametes - Transmitted to progeny and cause inherited disorders

53. Mutation-Types 1] By effect on structure Classified into: i . Large scale mutations Affect chromosomal structure Include: Amplifications/Gene duplications, Deletions, Chromosomal rearrangement (Chromosomal translocations, Chromosomal inversions ) ii. Small scale mutations Affect a gene in 1 or a few nucleotides If only 1 nucleotide is affected, they are called point mutations Include: Insertions, Deletions and Substitution mutations

54. Mutation-Types.. 2] By impact on protein sequence Classified into: i . Frameshift mutation Caused by insertion or deletion of a number of nucleotides that is not evenly divisible by 3 from a DNA sequence By contrast, any insertion or deletion that is evenly divisible by three is termed an  in-frame mutation ii. Point substitution mutation Results in a change in a single nucleotide Can be either synonymous or nonsynonymous

55. Mutation-Types.. Point substitution mutation: a] Synonymous substitution Replaces a codon with another codon that codes for same amino acid, so that the produced amino acid sequence is not modified If this mutation does not result in any phenotypic effects, then it is called  silent , but not all synonymous substitutions are silent b] Nonsynonymous substitution Replaces a codon with another codon that codes for a different amino acid, so that the produced amino acid sequence is modified Can be classified as nonsense or missense mutations

56. Mutation-Types Substitution Replacement of a single nucleotide by another MC type of mutation Deletion Involves loss of 1 or more nucleotides Insertion Involves addition of 1 or more nucleotides into a gene

57. GENETIC DISEASES

58. Origins of Medical Genetics In 1900 Mendel's work resurfaced His papers were quoted almost simultaneously by 3 European botanists De Vries (Holland), Correns (Germany) and Von Tschermak (Austria) - and this marked the real beginning of medical genetics, providing an enormous impetus for the study of inherited disease Credit for the first recognition of a single-gene trait is shared by William Bateson and Archibald Garrod , who together proposed that alkaptonuria was a rare recessive disorder

59. Problem caused by one or more abnormalities in the genome 4 types: Single-gene disorders : Mutation affects one gene Chromosomal disorders : Chromosomes (or parts of chromosomes) are missing or changed Polygenic disorders : Mutations in two or more genes. Often our lifestyle and environment also play a role Mitochondrial disorders

60. 1] Single gene disorders

61. Single gene disorders By 1966 almost 1500 single-gene disorders or traits had been identified, prompting the publication by an American physician, Victor McKusick , of a catalog of all known single-gene conditions By 1998, when the l2th edition of this catalog was published, it contained more than 8500 entries The growth of ' McKusick's Catalog' has been exponential and it is now accessible via the internet as Online Mendelian Inheritance in Man (OMIM) By mid-2006 OMIM contained a total of 16808 entries

62. Single gene disorders.. Histogram showing the rapid increase in recognition of conditions and characteristics (traits) showing single-gene inheritance

63. Result of a single mutated gene Over 16000 human diseases A trait or disorder that is determined by a gene on an autosome is said to show autosomal inheritance A trait or disorder determined by a gene on one of sex chromosomes is said to show sex-linked inheritance

64. Mode of inheritance Inherited in 5 ways: AD AR XD XR Y linked/ Holandric

65. i . Mendelian disorder-AD 1 dominant mutant gene is required to express disorder Both males and females Every generation When a parent is affected and the other is not, each offspring has a 50% probability of inheriting mutant allele and condition

66. Mendelian disorder-AD

67. Pedigree chart of autosomal dominant inheritance

68. Mendelian disorder-AD.. Achondroplasia Familial hypercholesterolemia Huntington’s disease Marfan syndrome Neurofibromatosis

69. ii. Mendelian disorder-AR Must be homozygous for mutant recessive genes to express the disorder Both parents must be heterozygous to transmit Probability: normal (25%), carrier (50%) and affected (25%) Both males and females Can skip generation

70. Mendelian disorder-AR

71. Mendelian disorder-AR.. Albinism Cystic fibrosis Wilson’s disease Inborn errors of metabolism ( Phenylketonuria , Maple syrup urine disease, Alkaptonuria , Lysosomal storage diseases) Sickle cell disease Thalassemia

72. iii. Mendelian disorder-XD Mutant dominant gene on X chromosome is required for disease expression Males as well as females are affected; Females are less severely affected Affected males can transmit disorder to their daughters but not to their sons

73. Mendelian disorder-XD Vitamin D resistant rickets Alport’s syndrome

74. iv. Mendelian disorder-XR Mutant recessive gene on X chromosome is required for disease expression Males - only affected Transmitted through carrier females Males cannot transmit disorder to their sons ie , no male to male transmission can occur

75. Mendelian disorder-XR Fragile X syndrome (MC) Haemophilia Partial color blindness Duchenne’s muscular dystrophy

76. v. Mendelian disorder-Y Y linked inheritance (trait) Males are only affected Affected males must transmit it to their sons Eg . Hairy ears, webbed toes

77. Pedigree chart of Y-linked disorder

78. 2] Chromosomal disorders

79. Chromosomal disorders Improved techniques for studying chromosomes led to the demonstration in 1959 that the presence of an additional number 21 chromosome ( trisomy 21) results in Down syndrome Other similar discoveries followed rapidly - Klinefelter and Turner syndromes - also in 1959 The identification of chromosome abnormalities was further aided by the development of banding techniques in 1970

80. Chromosomal disorders.. Most recently it has been shown that several rare conditions featuring learning difliculties and abnormal physical features are d/t loss of such a tiny amount of chromosome material that no abnormality can be detected using even the most high powered light microscope These conditions are referred to as microdeletion syndromes and are diagnosed using a technique known as FISH (fluorescent in situ hybridization) , which combines conventional chromosome analysis ( cytogenetics ) with much newer DNA diagnostic technology ( molecular genetics ) Increasingly, in the future, it is likely that the new technique of microarray CGH (comparative genomic hybridization) will play a large part in diagnosing these conditions

81. Very common Probably affect about half of all conceptions But most spontaneously miscarry, so frequency is about 1% 2 types: Numerical : Incorrect number of chromosomes in cells Structural : Change in structure of chromosome; eg . Cri du chat syndrome

82. Examples Numerical abnormalities: Autosomes : Down’s syndrome (21), Edward’s syndrome (18), Patau’s syndrome(13) Sex chromosomes : Turner’s syndrome (45 X0), Trisomy X, Klinefelter’s syndrome (47XXY), XYY male

83. Variations in the chromosomes number: Polyploidy: Presence of multiple of haploid number Of chromosomes other than diploid called polyploidy. Triploidy: Cells contain 69 chromosomes. Tetraploidy: Cells having 92 chromosomes. Aneuploidy : In this condition chromosome number is altered by one chromosome. Addition of one chromosome called trisomy . Loss of one chromosome called monosomy.

84. Chromosomal disorders- Mzm Nondisjunction Unequal separation of chromosomes in meiosis MC numerical chromosomal abnormality Result in 22 or 24 chromosomes in gametes

85. Chromosomal disorders- Mzm Mosaicism Nondisjunction of chromosomes during mitosis in early embryonic period Translocation Transfer of chromosome parts between non homologous chromosomes MC structural abnormality Deletion Loss of a portion of a chromosome

86. Down’s Syndrome Trisomy 21 1 in 800 live births Risk factors: Maternal age

87. Down’s Syndrome-C/Fs Flat facial profile, a somewhat depressed nasal bridge and a small nose; An upward slant to eyes; Enlargement of tongue MC genetic cause of mental retardation Fifth finger; Simian crease; Excessive space between large and second toe Heart defects Increased risk of leukemia; Alzheimer’s Sterility in all males

88. Down’s Syndrome

89. Edward’s Syndrome Trisomy 18 C/Fs: Mental retardation VSD Early death

90. Patau’s Syndrome Trisomy 13 C/Fs: Mental retardation Cleft lip and palate Polydactyly VSD Early death

91. Turner’s Syndrome 45 X0 C/Fs: Short stature Webbed neck Streak gonads Primary amenorrhea Delayed sex characters Shield like chest; widely placed nipples

92. Klinefelter’s syndrome 47 XXY C/Fs: Female secondary sex characteristics Testicular atrophy with azoospermia Learning difficulties Tall stature

93. Cri du chat syndrome Loss of short arm of chromosome 5 5p- syndrome C/Fs: Mental retardation Cat-like cry VSD

94. 3] Polygenic disorders

95. Polygenic disorders We now know that parameters such as height and skin color could be determined by the interaction of many genes, each exerting a small additive effect This is in contrast to single-gene characteristics in which the action of one gene is exerted independently, in a non-additive fashion This model of quantitative inheritance is now widely accepted and has been adapted to explain the pattern of inheritance observed for many relatively common conditions These include congenital malformations such as cleft lip and palate, and Iate -onset conditions such as hypertension, diabetes mellitus and Alzheimer disease

96. Polygenic Disorders Combination of multiple minor gene mutations plus environmental factors More common than Mendelian and chromosomal disorders DM, HTN, IHD, Schizophrenia, Asthma, Obesity

97. 4] Mitochondrial disorders

98. Aka maternal inheritance D/t dysfunctional genes in mitochondrial DNA Because only oocyte cells contribute mitochondria to developing embryo, only mothers can pass on mitochondrial conditions to their children Eg .  Leber's hereditary optic neuropathy, Mitochondrial encephalopathy

99. Pedigree charting of mitochondrial disorder

100. Acquired somatic genetic disease Not all genetic errors are present from conception Many billions of cell divisions (mitoses) occur in the course of an average human lifetime During each mitosis there is an opportunity for both single-gene mutations to occur, because of DNA copy errors, and for numerical chromosome abnormalities to arise as a result of errors in chromosome separation Accumulating somatic mutations and chromosome abnormalities are now known to play a major role in causing cancer , and they probably also explain the rising incidence with age of many other serious illnesses, as well as the aging process itself It is therefore necessary to appreciate that not all disease with a genetic basis is hereditary

101. EMBRYOLOGY

102. Study of development of human organism from conception till birth in maternal womb Development is divided into 3 periods: 1. Pre-embryonic period : Conception - 2 weeks 2. Embryonic period : 3 rd week – 8 th week 3. Fetal period : 9 th week – Birth

103. Fertilization

104. Fusion of male and female gametes Only 1% of the total sperm deposited in the vagina enter the cervix It takes around 2-7 hrs for sperms to reach oviduct from cervix In the ampullary region of oviduct

105. For fertilization to occur sperm must undergo following changes Capacitation Acrosomal reaction

106. Capacitation Functional changes that causes tail of sperms to beat vigorously Removal of glycoprotein coat and seminal plasma proteins from plasma membrane that overlies acrosomal region of spermatozoa

107. Acrosome reaction

108. Acrosome reaction

109. Acrosome reaction

110. Acrosome reaction

111. Phases of fertilization Phase 1: penetration of corona radiata Phase 2: penetration of zona pellucida Phase 3: fusion of oocyte and sperm cell membranes

112. Response of oocyte after penetration of spermatozoa Cortical and zonal reaction Resumption of second meiotic division Metabolic activation of egg

113. Results of fertilization Restoration of diploid chromosome number. Half from the mother, half from the father. Determination of chromosomal sex. Initiation of cleavage

114. Cleavage Cleavage: repeated mitotic divisions of zygote. Cell number increases without increase in size Blastomeres : smaller cells produced by cleavage 1 st division of zygote – after 24hrs of fertilization 16 cell morula (day 4 fertilization)

115. Cleavage divisions

116. Compaction (at 8 cell stage) After 3 rd cleavage Blastomeres maximize contact with each other, forming a compact ball of cells

117. The blastocyst Embryonic pole Abembryonic pole

118. Transport of fertilized oocyte From ampulla of fallopian tubes (site of fertilization) to the body of uterus (site of implantation) Takes about 5 days Mechanisms involved: Ciliary action of fallopian tube epithelium Muscular action of fallopian tube

119. Implantation Blastocyst adheres to uterine mucosa on 6 th post ovulatory day Implantation includes the following stages: dissolution of the zona pellucida (hatching) orientation and adhesion of the blastocyst onto the endometrium trophoblastic penetration into the endometrium migration of the blastocyst into the endometrium spread and proliferation of the trophoblast

120. SECOND WEEK OF DEVELOPMENT

121. Features seen in the second week Differentioation of embryoblast: Formation of bilaminar germ disc: epiblast and hypoblast Differentiation of trophoblast: syncytiotrophoblast and cytotrophoblast Differentiation of cavity: amniotic cavity and primitive yolk sac Also known as period of two.

122. DAY 8 Blastocyst is partially embedded Cytotrophoblast and syncytiotrophoblast Hypoblast layer and epiblast layer A cavity appears within the epiblast cells and expands to form amniotic cavity

123. DAY 9 More deeply implanted Penetration defect - Fibrin plug Syncytiotrophoblast develop vacuoles – merge forming lacunae {Lacunar stage} Hypoblast cells line blastocyst cavity- Heuser’s (Exocoelomic) membrane Now called Primitive yolk sac (Exocoelomic cavity)

124. DAYS 10-12 Completely embedded Defect lined by epithelium Blood from maternal dilated capillaries (sinusoids) enter syncytial lacunar system as syncytiotrophoblast invade sinusoids Uteroplacental circulation

125. DAYS 10-12 Extraembryonic mesoderm fills space between trophoblast (externally) and amnion and exocoelomic membrane (internally) Extraembryonic cavity (Chorionic cavity) divides extraembryonic mesoderm into somatic and splanchnic layers Decidua reaction

126. DAYS 13 Second wave of cells from hypoblast lines primitive yolk sac – Definitive/Secondary yolk sac Exocoelomic cavity (Primitive yolk sac) – Pinched off – Exocoelomic cysts Chorionic cavity expands Extraembryonic mesoderm lining cytotrophoblast - Chorionic plate

127. DAYS 13 Trophoblast is characterized by villous projections (Primary villi)

128. CLINICAL CORRELATES-2 nd WEEK Abnormal implantation Hyadatidiform mole ( partial, complete, and invasive mole)

129. EMBRYONIC PERIOD

130. Main organ systems – established by end of emb pd Period of organogenesis Each germ layer - Specific tissue and organs

131. Most congenital anomalies are produced by teratogens acting during this period

132. THIRD WEEK OF DEVELOPMENT:TRILAMINAR GERM DISC

133. Major Events Gastrulation Formation of 3 new structures 1. Primitive streak 2. Notochord 3. Neural tube

134. GASTRULATION

135. Begins with formation of primitive streak on dorsal caudal aspect of epiblast Establishes all three germ layers

136. Many epiblast cells migrate towards streak Detach from epiblast , and slip beneath it ( Invagination )

137. During invagination some cells: Displace hypoblast Endoderm Others come to lie between epiblast and newly created endoderm Intraembryonic mesoderm Remaining cells in the epiblast Ectoderm

138. 3 germ layers give rise to all the tissues of the body

139. Therefore the epi-blast cells through the process of grastrulation , become the source of all germ layers Because of fusion of ecto & endoderm buccophryngeal membrane and cloacal membrane are formed

140. A circular thickening appears in the hypoblast caudal to primitive streak in the midline to form the cloacal membrane , the future site of the anus

141. CLINICAL CORRELATES

142. Clinical Correlates Cau dal dysgenesis ( Sirenomelia ) D/t disruption of gastrulation by genetic abnormalities and toxic insults Insufficient mesoderm is formed in the caudal most region of the embryo

143. PRIMITIVE STREAK

144. Thickening of part of epiblast At its cephalic end - a knob-like thickening - primitive node [ Hensen’s node ] appear whose centre has a pit “ primitive pit ”

145. Sacrococcygeal teratoma Remnants of primitive streak

146. NOTOCHORD

147. Prechordal plate is the site of future mouth Oropharyngeal memb , which is a bilaminar (ectoderm and endoderm) membrane, is derived from prechordal plate 2 nd wk : Cell layers between epiblast and hypoblast are separable except at a point called prechordal plate Prechordal plate also determines the polarity of bilaminar germ disc

148. Notochord defines the body axis and it is future site of vertebral column Prenotochordal cells from epiblast migrate through primitive streak and invaginate

149. Become intercalated in endoderm transiently and form notochordal plate Detach from endoderm and form a solid cord of cells k/a notochord

150. Extend: Cranially to prechordal plate Caudally to primitive pit Forms nucleus pulposus of IV disc

151. Formation of notochord..

152. Formation of notochord.. At the point where the pit forms an indentation in epiblast , neurenteric canal temporarily connects amniotic and yolk sac cavities

153. NEURULATION

154. FORMATION OF NEURAL PLATE

155. FORMATION OF NEURAL GROOVE

156. FORMATION OF NEURAL TUBE

157. The cranial ⅓ of the neural tube represent the future brain The caudal ⅔ represents the future spinal cord

158. Congenital Anomalies of the Nervous System Disturbance of neurulation may result in severe abnormalities of the brain and the spinal cord Most defects are the result of non-closure or defective closure of the neural tube: In the brain region (e.g. anencephaly) In the spinal cord regions (e.g. spina bifida) High level of alpha-fetoprotein (AFP) in the amniotic fluid is a strong sign of neural tube defects

159. GERM LAYERS-DERIVATIVES

160. DERIVATIVES - ECTODERM Surface ectoderm Neuroectoderm

161. Surface Ectoderm Epidermis of the skin Hair Nail Sweat & Sebaceous glands Mammary glands Enamel of the teeth Lens of eye Internal ear Anterior lobe of the pituitary gland

162. Neural crest cells Craniofacial skeleton Neurons for cranial ganglia Glial cells Melanocytes

163. Neural crest cells Melanocytes Sensory ganglia Sympathetic and enteric neurons Schwann’s cells Cells of adrenal medulla

164. Ectodermal germ layer gives rise to organ and structure that maintain contact with outside world : T he central nervous system T he peripheral nervous system T he sensory epithelium of ear, nose, and eye. T he epidermis including the hair and nail In addition it gives rise to: S ubcutaneous glands T he mammary glands T he pituitary glands E namel of the teeth

165. CLINICAL CORRELATES NEURAL TUBE DEFECTS Occurs when neural tube closure fails to occur Anencephaly Spina bifida 50-70%: Folic acid

166. DERIVATIVES - MESODERM Paraxial mesoderm Lateral plate mesoderm Intermediate mesoderm

167. Paraxial mesoderm Thick plate of mesoderm on each side of midline Organized into Somitomeres 1 st – Cephalic region Cephalocaudally CRANIAL region A/w segmentation of neural plate – Neuromeres Mesenchyme in head region

168. Also, cells from ventrolat Migrate to parietal layer of lateral plate Musculature for body wall and limbs Cells of Dermomyotome Dermis of back Muscles of back, body wall Some limb muscles

169. Intermediate mesoderm Temporarily connects paraxial and lateral plate mesoderm Urogenital structures (Not bladder)

170. Lateral plate mesoderm Splits into Parietal (Somatic) mesoderm layer – Intraembryonic cavity Visceral (Splanchnic) mesoderm layer – Surrounds organs