Embryology-Nervous System Development

EmbryologyNervous system

development

M. K. TadjudinFakultas Kedokteran dan Ilmu Kesehatan

Universitas Islam Negeri Syarif HidayatullahJakarta

2

Learning Objectives

• Understand the structures derived from ectoderm.

• Understand the formation of neural folds. • Identify the initial location of neural crest cells

in the trilaminar embryo. • Identify pathways of neural crest migration

throughout the embryo. • To know the major tissues to which neural crest

cells contribute. • To know how abnormalities in development

that result from abnormal neural crest cell migration.

• Understand how neural crest cells contribute to the pharyngeal arches and the head structures they form.

3

Neural development is one of the earliest to begin and the last to be complete, generating the most complex structure within the embryo. This long time period of development also means any in utero insult during pregnancy may have consequences to development of the nervous system.

4Ontogeny tends to recapitulate phylogeny (Haeckel)

5

6

7

8

9

10

11

Zygote with 2 pronuclei

12

Cleavage

13

Zigot

Blastosis

Morula

14

Inner cell mass

15

Bilaminar disk, amniotic cavity and primary yolk sac • During implantation, a cavity appears in the inner

cell mass; amnion forms around this amniotic cavity; derived from amnioblasts from the epiblast

• Cells of the embryonic disc flatten and differentiate into two layers:-epiblast - a tall, columnar layer of cells forming the "floor" of the amniotic cavity (primitive ectoderm)-hypoblast - a short, cuboidal layer of cells forming the "roof" of the exocoelomic cavity (primitive endoderm)

• The exocoelomic cavity and membrane form the primary yolk sac

• Thus, bilaminar embryonic disk is sandwiched between two "balloon-like" cavities, the amniotic cavity and the primary yolk sac

16

17

Extra-embryonic mesoderm/Extra-embryonic

coelom • Cells derived from the primitive ectoderm

fill the space between the trophoblast and two cavities

• This loose connective tissue, the extra-embryonic mesoderm, completely surrounds the amnion and primary yolk sac

• Fluid-filled spaces appear in the mesenchyme, pushing aside the mesenchyme to form a coelom

• These spaces fuse to form a fluid-filled cavity completely surrounding the amnion and yolk sac, except at the connecting stalk

18

19

20

Formation of the chorion and definitive yolk sac (1)

• Endodermal cells from the hypoblast migrate to the primary yolk sac

• As the extra embryonic coelom grows, the large primary yolk sac pinches off, leaving behind a smaller, secondary yolk sac which is "permanent"

• The extra embryonic fluid is actually surrounding the entire amnion and yolk sac, except at the connecting stalk

21

Formation of the chorion and definitive yolk sac (2)

• The extra-embryonic coelom (future chorionic cavity) separates the extra-embryonic somatic mesoderm (lining the trophoblast and amnion) from the extra-embryonic splanchnic mesoderm (lining the yolk sac only)

• The embryo, surrounded by two cavities, floats in a large "bubble" (future chorionic cavity)

22

23

Summary of Origin of Extraembryonic Membranes

 AMNION bilayer amniotic epithelium +

extraembryonic somatic mesoderm

 CHORION trilayer

 extraembryonic somatic mesoderm + cytotrophoblast + syncytiotrophoblast

 YOLK SAC WALL bilayer yolk sac endoderm +

extra-embryonic splanchnic mesoderm

24

25

Gastrulation (1)• Conversion of the bilaminar to a trilaminar

embryonic disk• INITIATED BY THE PRESENCE OF THE

PRIMITIVE STREAK, a raised layer on the surface of the epiblast proliferating and migrating caudally and cranially it ending in the primitive node

• From this point on, one can identify the cranial/caudal ends, the dorsal/ventral sides, and right from left

• Cells then migrate between the hypoblast and epiblast to form intra-embryonic mesenchyme, a loose embryonic connective tissue

26

Gastrulation (2)• Cells also migrate to the hypoblast where

they become the intra-embryonic endoderm• Cells that remain in the epiblast form the

future ectoderm, the middle layer becomes the mesoderm, and the hypoblast becomes the endoderm

• Cells then migrate from the primitive streak to other sites where they will undergo further differentiation

• Some will travel cranially to form the notochord, some laterally, to become continuous with the extra-embryonic mesenchyme, and those most cranially will form the cardiogenic mesenchyme (future heart)

27

Late in the second week of human gestation, the embryo has two cell layers, an epiblast and a hypoblast.

28

Primitive streak

29

30

The epiblast cells at the caudal midline (PRIMITIVE STREAK) invaginateThis process is termed GASTRULATION (16 days)

31

Invagination of these cells results in formation of the mesoderm and replacement of some of the hypoblast cells to produce the definitive endoderm (16 days)

32

                 A cut through the embryo illustrates the three germ layers: ectoderm (formerly referred to as epiblast), mesoderm, and endoderm (17 days)

33

Primitive streak (1)

• The primitive streak appears on the epiblast surface, migrating caudally from the primitive node (Hansen's node) to the cloacal membrane where it stops; it grows by the addition of cells at the "tail" end

• Embryonic orientation established: cranial/caudal since primitive streak migrates caudally, right vs. left, and dorsal vs. ventral since primitive streak occurs on dorsal side

34

Primitive streak (2)

• Cells migrate from the epiblast to the middle layer between it and the hypoblast; forming intra-embryonic mesenchyme (loose embryonic connective tissue)

• Mesenchymal cells migrate from primitive streak cranially to form (1)cardiogenic mesenchyme (most cranial point), (2)the notochordal process (also in the cranial direction), and (3)lateral mesenchyme (to the lateral edges where it meets with extra-embryonic mesenchyme)

35

Primitive streak (3)

• Cells migrate from the epiblast to the middle layer between it and the hypoblast; forming intra-embryonic mesenchyme (loose embryonic connective tissue)

• Mesenchymal cells migrate from primitive streak cranially to form (1)cardiogenic mesenchyme (most cranial point), (2)the notochordal process (also in the cranial direction), and (3)lateral mesenchyme (to the lateral edges where it meets with extra-embryonic mesenchyme)

36

Primitive streak (2)

• The length of the primitive streak will decrease as the notochord increases and it will eventually degenerate, so that the caudal end of the embryo will decrease in size

• If the primitive streak does not degenerate, this undifferentiated tissue could result in a sacro-coccygeal teratoma

37

                    The cardiogenic (heart) region is rostral to the prechordal plate. The prechordal plate is at the site of the developing oral cavity. (17 days)

38

The notochord extends in the midline from the prechordal plate, caudally to the primitive streak

39

                A sagittal cut through the cranial end of the embryo(19 days)

40

As the neural cells proliferate and grow forward, the cardiogenic area is folded over and the endoderm-lined foregut is formed (19 days)

41

Oral cavity

Stomadeum

42

         The prechordal plate contributes to the tissues that separate the stomadeum and foregut. This tissue is referred to as the buccopharyngeal membrane and consists of ectoderm opposed to endoderm.

43

44

• The notochordal process develops by the migration of mesenchymal cells cranially from the primitive node, eventually stopping at the bucco-pharyngeal membrane (a bilayer disk of endoderm/ectoderm)

• The floor of the notochordal process fuses with the intra-embryonic endoderm of the yolk sac

• The fused layers degenerate temporarily to form a transitory communication with the yolk sac (neurenteric canal)

Notochord (1)

45

• The notochordal plate folds inward, to form a rod-shaped notochord; cell proliferation occurs cranially to caudally

• As the notochord closes as a tube, it detaches from the endoderm of the yolk sac

• It is now located in the mesoderm, between the endoderm and ectoderm

Notochord (2)

46

Notochord (3)• A solid aggregation of mesenchyme • Grows cranially eventually reaching

from the primitive node (one end point of the primitive streak) to the bucco-pharyngeal membrane (future mouth)

• As the notochord joins the endoderm, it will form a temporary communication between the amniotic cavity and the yolk sac, permitting amniotic fluid to circulate in the neurenteric canal.

47

Notochord (4)• As the notochord grows cranially,

the size of the primitive streak should diminish cranially, until it eventually disappears.

• The notochord then plays an important role, as the primary inducer of the neural tube through the release of cytokines and growth factors.

48

49

Functions of the Notochord

1. STRUCTURE - acts as a rigid axis around which the embryo develops

2. SKELETAL - foundation upon which the vertebral column (vertebral bodies) will form

3. INDUCTION - will bring about formation of the neural tube (future nervous system)

Fate of notochord: It will eventually break up into section of weight-bearing intervertebral disks, known as the nucleus pulposus (this little structure may give rise to what is commonly known as a "slipped disk." A tumor can occur here, known as a chordoma, localized in the intervertebral disk, capable of causing nerve damage.

50

Neurulation (1) • Neurulation includes the formation of the

neural plate (day 18-19), neural folds (day 20-21), and the neural tube (day 22-26); the latter will develop into the future brain and spinal cord

• The neural plate forms as a central strip of surface ectoderm cells, just above the notochord. It is induced to become neuroectoderm through changes in cell shape (cuboidal to columnar) and proliferation; the cells develop N-CAM adhesion molecules, disorganized filaments and elongated tubules; this flat layer of cells is referred to as the neural plate

51

Neurulation (2) • The layer of cells between the regular surface

ectoderm and the neuroectoderm possess characteristics of both cell types, such as the possession of both L-CAM (ectoderm) and N-CAM (neuroectoderm) adhesion molecules, and are called neural crest cells.

• At the neural plate, the cells continue to morph into pyramidal shaped cells with straight neuro-tubules, neuro-filaments concentrated at the apex of the cell, connected by desmosomes

• The change in cell shape and a decrease in cell number cause the neuroectodermal cells to gradually fold inward, forming neural folds (d 20-21)

52

Neurulation (3) • The neural tube continues to grow in this

manner, and eventually breaks free of the surface ectoderm which will be sealed off. Up to this point, it was supplied continuously with amniotic fluid

• As the neural tube forms, the closing process is critical, occurring from the cranial to the caudal end as the anterior neuropore closes around day 24, the posterior around day 26. This is a critical event, as defects in closure may result in spina bifida or other neural tube defects. The risk of a neural tube defect can be decreased by folic acid supplements

53

Neurulation (4) • The neuroepithelial cells at this

stage are bipotential, capable of forming neurons or neuroglial cells.

• Once the neural tube has closed completely, vertebral structures develop around it, as do meninges and finally, skin from the surface ectoderm

54

55

Neural tube

formation

56

57

58

Neural Crest Cells Derivatives

• As the notochord induces the transformation of surface ectoderm to neuroectoderm, a multipotential middle cell layer develops with characteristics of both cell types (N-CAM and L-CAM adhesion molecules) as well as important future roles.

• These neural crest cells migrate dorsolaterally to form the neural crest, a flattened irregular mass between the surface ectoderm and neuroectoderm

• This layer will separate into right and left portions and then migrate to different areas

59

Neurulation-review

• The notochord is of mesenchymal origin• During formation, it is continuous with

embryonic endoderm, allowing for the neurenteric canal between the amniotic and yolk sac cavities

• The notochord then detaches from the endoderm to form a closed tube in the mesoderm

• On the other hand, the neural tube originates from the ectodermal layer, when the surface ectoderm is induced by the notochord to form neuroectoderm

• Thus, the neural tube begins its development intercalated in the primitive ectoderm but, like the notochord, eventually detaches to form a closed tube

60

Neurulation-review

• The notochord is of mesenchymal origin• During formation, it is continuous with

embryonic endoderm, allowing for the neurenteric canal between the amniotic and yolk sac cavities

• The notochord then detaches from the endoderm to form a closed tube in the mesoderm

• On the other hand, the neural tube originates from the ectodermal layer, when the surface ectoderm is induced by the notochord to form neuroectoderm

• Thus, the neural tube begins its development intercalated in the primitive ectoderm but, like the notochord, eventually detaches to form a closed tube

61

4 Week Embryo (1)

• In week 4, the embryo undergoes major morphological changes as it changes from a trilaminar disk-shaped embryo to a cylindrical embryo

• This is also an important week in terms of determining placement of future organs

• Following median and horizontal folding, many organs and body cavities will begin to form or will be repositioned

62

4 Week Embryo (2)

• At the beginning of week 4, the embryo is 2.0-3.5 mm long, straight, has 4-12 somites, and a neural tube that has begun to close at the cranial end (rostropore)

• Somites will continue to develop, increasing in number to 20-30 during this week, the somite period of development

• They can be visualized on the surface of the embryo and are used to estimate the age of the embryo

• They will eventually give rise to the vertebrae, ribs, and musculature of the axial skeleton, as well as the dermis.

63

4 Week Embryo (3)

• A horseshoe shaped intraembryonic coelom forms as coelomic spaces in the lateral plate mesoderm and cardiogenic mesenchyme came together at the end of the third week

• This coelom will provide a space for the development and necessary movement of organs

• It will form the future pericardial, pleural and peritoneal cavities. and also provides the framework for the future body wall or somatopleure, composed of surface ectoderm, lateral plate mesenchyme and a mesothelial lining, which lines the amnion, as well as the future gut wall, splanchnopleure, of endoderm, lateral plate mesenchyme and mesothelium around the yolk sac

• The mesothelial linings of these walls will eventually form the visceral and parietal layers of the various cavities.

64

4 Week Embryo (4)• At the end of week 3, spaces in the lateral plate

and cardiogenic mesenchyme fuse to form a horseshoe-shaped intra-embryonic coelom (same process of development as the extra-embryonic coelom)

• Amniotic fluid can then circulate in this area, as it communicates with the extra-embryonic coelom

• The curve of this horseshoe will form the pericardial cavity and the limbs will form the future pleuroperitoneal cavities

• In the fourth week, the horseshoe will change to a pericardial cavity, with two symmetrical pericardioperitoneal canals, leading to the large peritoneal cavity

65

4 Week Embryo (5)• The future body wall is formed on the dorsal

surface of the cavity of somatic mesoderm from the lateral plate, mesothelium, and surface ectoderm

• The future gut wall is formed from lateral plate mesoderm, mesothelium and endoderm on the ventral surface of the intra-embryonic coelom

• During this week, the embryo will fold laterally, so the outer somatopleure envelops the inner splanchnopleure

• The three body cavities (pericardial, pleural, peritoneal) will form definitively in the second month.

66

67

68

Somite Development (1)

• Somites are segmented blocks of mesoderm that will give rise to the body and limb muscles, vertebral column, and the dermis.

• At the end of week 3, the intra-embryonic mesenchyme differentiates into three loose aggregate pairs of mesenchyme on each side of the neural tube

• Medially, the paraxial mesoderm differentiates into the future dermatome (dorsal surface), myotome (middle layer), and sclerotome (ventral layer), forming dermis, muscle, and connective tissue respectively

• Moving laterally, the second aggregate pair, called the intermediate mesoderm, will form the future urogenital system

69

Somite Development (2)

• Most laterally, the lateral plate mesoderm will develop into future body cavities (intraembryonic coelom) and parts of the body wall.

• The paraxial mesoderm will develop into paired cuboidal bodies, or somites (Gr. soma, body)

• These will eventually develop into the bones (sclerotome), muscles (myotome), and dermis (dermatome) of and surrounding the axial skeleton

• Somites appear as bumps on the dorsal surface of the embryo

• At the end of week 3, 4-12 somites are present (visible on the dorsal surface of the embryo).

• By the end of week 5, 42-44 can be counted. However, most appear between days 20-30, giving this period the title of the somite period of development

70

Somite Development (3)

• Somites appear cranially to caudally, beginning at the occipital end

• They can be counted and are used to roughly estimate the age of the embryo

• Eventually, they play a major role in segmentation of the embryo and the adult. Since several somites will disappear, the final number is 31 pairs of somites.

• Law of Original Innervation: The myoblasts (future muscle cells) form concurrently with the spinal nerves and they migrate out from the notochord together.

• This results in the formation of 31 spinal nerves with associated skin, muscle, and connective tissue.

71

72

Dorsal View of an Embryo at about 22 days (8 somite stage)

73

Head-Tail Folding • Due to the rapid growth in the median plane of the

brain, amniotic cavity, and somites, the embryo elongates, with its head and tail ends folding under

• At the cranial end, the head will be folded under, with a very prominent forebrain.

• Just cranial to it, on the ventral side, will lie the newly positioned primitive heart, pericardial cavity, septum transversum, and bucco-pharyngeal membrane

• During this fold the future body cavities of the intra-embryonic coelom will find their future locations and the foregut will form from the endoderm of the yolk sac, resulting in a reduced yolk sac.

• At the tail end, the endoderm of the yolk sac is incorporated into the embryo to form the hindgut region.

• The connecting stalk is now attached ventrally, with the allantois jutting into the embryo

74

75

76

77

Lateral Folding • At the same time that head-tail folding is

occurring, lateral folding is also occurring to form a cylindrical embryo

• The layers of the somatopleure surrounding the amnion grow downwards to enclose the gut with its splanchnopleure

• The endoderm of the yolk sac forms the future midgut, connected to the yolk stalk

• The folding results in the formation of the umbilical cord, amniotic epithelium surrounding all the middle layers that were enclosed during the folding process (extra-embryonic mesenchyme primarily, also part of the yolk sac, allantois and extra-embryonic coelom)

78

79

At this stage, the embryo curves ventrally, bringing the cranial and caudal ends of the embryo close together. The ventral curvature and continued growth result in narrowing of the connection between the gut and the yolk sac, forming the vitelline duct.

80

In this embryo the vitelline duct was cut when the embryo was separated from the yolk sac. (25 days)

81

The posterior neuropore closes about 2 days after the anterior neuropore, when the embryo is tightly curved ventrally and an upper limb bud is evident (28 days)

82

83

84

85

86

87

88

89

The epiblast cells at the caudal midline (PRIMITIVE STREAK) invaginateThis process is termed GASTRULATION (16 days)

90

Invagination of these cells results in formation of the mesoderm and replacement of some of the hypoblast cells to produce the definitive endoderm (16 days)

91

                 A cut through the embryo illustrates the three germ layers: ectoderm (formerly referred to as epiblast), mesoderm, and endoderm (17 days)

92

The ectoderm can be distinguished as neural ectoderm that comprises the central nervous system, and surface ectoderm that will cover the outside of the body. (17 days)

93

By the beginning of the 4th week of human development, a ventral view illustrates several important structures:the anterior-most aspect of the brain (forebrain, prosencephalon),the heart (which is just beginning to beat),the foregut region dorsal to the heart,and the developing hindgut.(22 days)

94

The neural folds fuse, forming the portion of the neural tube that will be the brain and the spinal cord (22 days)

95

Fusion of the neural folds is initiated at the future upper cervical levels, progressing both rostrally and caudally to form the neural tube.(23 days)

96

A Ventral view illustrates:the stomadeum (primitive oral cavity), the heart in the pericardial cavity,the anterior intestinal portal leading to the foregut,and the posterior intestinal portal leading to the hindgut.(23 days)

97

Closing anterior neuropore and the stomadeum.

98A cross-section of the fused neural tube (28 days)

99

Pseudostratified epithelial cells of the neural tube, with the nuclei of dividing cells being located at the lumenal surface

100

At a more advanced stage, the cells opposite the lumenal border begin to differentiate

101

Following fusion of the neural folds, neural crest cells leave the dorsal aspect of the developing spinal cord to form the sensory neurons of the spinal (dorsal root) ganglia (28 days)

102

The spinal (dorsal root) ganglia are located just lateral to the neural tube (6 weeks)

103

The cells of the neural tube form three layers, a ventricular layer of undifferentiated, proliferating cells, a mantle layer of differentiating neurons that will form the gray matter of the spinal cord, and a marginal layer that contains nerve fibers and will be the white matter (6 weeks)

104

The dorsal portion of the neural tube is termed the alar plate and forms the sensory area; the ventral portion is termed the basal plate and forms the motor area of the spinal cord

105

Motor axons grow out from the neurons in the basal plate, while cells in the dorsal root ganglia extend sensory fibers both centrally and peripherally

106

Following the closure of the trunk neural folds, the neural crest cells leave the dorsal aspect of the neural tube. (22 days)

107

A cut through the recently closed cranial neural tube illustrates the forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon) (5 weeks)

108

The prosencephalon has two subdivisions, the telencephalon: that will form the cerebral hemispheres, and the diencephalon: that will form optic and thalamic tissues and other structures.

109

A dorsal view of the hindbrain, following removal of the thin roof of the fourth ventricle, illustrates the cerebellar plate (6 weeks)

110

A dorsal view illustrates the midbrain (mesencephalon), hindbrain (rhombencephalon), and neural folds that remain unfused. Also note the region of the primitive streak.(22 days)

111

The mesencephalon is not subdivided, while the rhombencephalon is divided into the metencephalon: and the myelencephalon: In the rhombencephalon, subsegments termed rhombomeres are apparent, as is the thin layer of cells at the dorsal-most aspect of this brain region

112

A cut through the myelencephalon illustrates the thin roof plate as well as the alar and basal plate regions, all of which surround the lumen, which at this level forms the fourth ventricle of the brain (9 weeks)

113

The tissue of the metencephalon will form the cerebellum and the pons. The alar and basal plates of the myelencephalon are also evident (6 weeks)

114

By the beginning of the fetal period, the cerebellar plate begins to acquire differentiated cell types. The choroid plexus projects into the roof of the fourth ventricle.(9 weeks)

115

            The hypophysis or pituitary gland is derived, in part from an ectodermal outpocketing of the stomadeum (Rathke's Pouch) and in part from the floor of the diencephalon (infundibulum) (5 weeks)

116The adenohypophysis (anterior lobe) is derived from Rathke's Pouch and the neurohypophysis (pars nervosa) is derived from the infundibulum

117

                Development of the diencephalon also entails formation of the hypothalamus and thalamus (9 weeks)

118

          The rostral-most portion of the prosencephalon, the telencephalon, expands posteriorly and laterally as the cerebral hemispheres (9 weeks)

119

      A cut through the forebrain at the level of the line illustrates the expanding cerebral hemispheres surrounding the lateral ventricles; the third ventricle; hypothalamus; infundibulum; and corpus striatum (6 weeks)

120

Further expansion, the cereberal hemispheres cover the lateral aspect of the diencephalon, mesencephalon and the rostral portion of the metencephalon.

121

Early in the fourth week of human development the cranial and cervical (neck) regions make up approximately 1/2 of the embryo's length. (22 days)

122

The developing face is represented by the frontonasal region, and the first pharyngeal (branchial, visceral) arch.(22 days)

123

Arrows indicate the origin and destinations of neural crest cell populations. In the facial region neural crest cells contribute all of the skeletal and connective tissues with the exception of tooth enamel.

124

Neural crest cells form the majority of the facial and cranial skeleton. However, mesodermal cells also contribute to the cranium.

125

Visceral arches and clefts

• Gill arch and clefts• Located in the pharyngeal part of the

digestive tract behind the oral cavity and anterior to the esophagus

• The visceral clefts appear as several pairs of pouches that push outward from the lateral walls of the pharynx eventually to reach the surface to form the clefts

• The clefts are continuous, slit-like passages connecting the pharynx to the exterior

• The soft and skeletal tissues between adjacent clefts are the visceral arches

• The embryonic fate of the clefts and slits varies greatly depending on the taxonomic subgroup.

126

127

The pharyngeal arches are organized around blood vessels that extend dorsally from the developing heart. (23 days)

128

Five pairs of aortic arch vessels form temporally in a cranial to caudal sequence. The cranial-most vessels regress as the caudal ones develop

129Aortic arches

130

The regions between the pharyngeal arches are termed pharyngeal clefts. The indentation just dorsal to the second pharyngeal cleft is the developing inner ear, the otic pit.(27 days)

131

The first pharyngeal arch has both a maxillary and a mandibular prominence. Dorsal to the first arch is an elevation formed by the underlying trigeminal ganglion, the sensory ganglion for the nerve that supplies tissues derived from the first arch. (29 days)

132

Each of the pharyngeal arches is supplied by a specific cranial nerve.The cells that contribute to the sensory ganglia are derived from neural crest cells and from epibranchial placodes.

133

Epibranchial placodes are specialized regions of surface ectoderm, the cells of which invaginate to contribute to the formation of the sensory ganglia of cranial nerves V, VII, IX, and X. (29 days)

134

The buccopharyngeal membrane begins to break down at this stage to allow continuity between pharynx and the stomodeum (primitive oral cavity).(28 days)

135

Remnants of the buccopharyngeal membrane are seen between the stomodeum and the pharynx, separating the ectodermally and endodermally covered portions of the first pharyngeal arch.

136

Closing membranes, consisting of ectoderm, opposed to endoderm, separate the pharyngeal clefts from the pouches.Each arch contains mesenchyme that is derived in part from neural crest and in part from mesoderm. (29 days)

137

Buccopharyngeal membrane remnant and the dorso-ventral extent of the first and second pharyngeal pouches.(5 weeks)

138

At a slightly later developmental stage, four pouches are evident.

139Derivatives of the pharyngeal pouches

140

Some of the neural crest cells in each of the arches become cartilage.

141

The pharyngeal arches contribute to the developing tongue and epiglottis

142

The frontonasal prominence is composed of the tissue that surrounds the forebrain. (5 weeks)

143

Following closure of the anterior neuropore, the ectoderm that will line the nasal cavities (olfactory placodes) is located on the lateral aspects of the frontonasal prominence. (5 weeks)

144

In the fifth week of human gestation, the olfactory placodes line the nasal pits. Medial and lateral nasal prominences form around the nasal pits. (5 weeks)

145

Union of the medial nasal prominence with the lateral nasal prominence and maxillary prominence is required for normal development of the upper lip. (6 weeks)

146

The medial nasal prominences merge in the midline to smooth the median furrow. (6 weeks)

147

Contribution of each of the prominences to the face

148

The secondary palatal shelves (outlined) are considered to be part of the maxillary prominences. (6 weeks)

149

The medial nasal prominences contribute the tissues that will form the anterior part of the palate, the primary palate (circled). (7 weeks)

150

The oronasal membrane breaks down to allow continuity between the nasal pit and the common oral and nasal cavities.

151

A frontal cut illustrates that the tongue is initially interposed between the secondary palatal shelves. (8 weeks)

152

The palatal shelves become positioned above the tongue to allow for fusion in the midline. (9 weeks)

153

Fusion of the palatal shelves with each other and with the nasal septum separates the nasal cavities from the oval cavity. (10 weeks)

154

The four maxillary incisors develop within the primary palate.(10 weeks)

155

156

157

http://www.med.unc.edu/embryo_images/unit-bdyfm/bdyfm_htms/bdyfm014.htm