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Contents Section I: Embryology Chapter 1. Gametogenesis .............................................. 3 Chapter 2. Fertilization ................................................. 7 Chapter 3. First Week .................................................. 9 Chapter 4. Second Week .............................................. 11 Chapter 5. Third Week ................................................ 15 Chapter 6. Fourth to Eighth Weeks ...................................... 19 Chapter 7. Ninth Week to Parturition .................................... 25 Chapter 8. Fetal Membranes and Placenta ................................ 29 Chapter 9. Body Cavities and Mesenteries ................................ 35 Chapter 10. Pharyngeal Arches and Their Derivatives ....................... 39 Chapter 11. Congenital Abnormalities .................................... 45 Section II: Histology Chapter 1. Epithelium ................................................. 53 Section III: Pathology Chapter 1. General Pathology .......................................... 61 KAPLAlf I me d lea vii Section IV: Pharmacology Chapter 1. Pharmacodynamics and Pharmacokinetics ..................... 85 Chapter 2. Autacoids ............................................... 95 Chapter 3. Lead Toxicity and Chelating Agents .......................... 113 Chapter 4. Antineoplastic Agents ..................................... 117 Section V: Behavioral Sciences Chapter 1. The Basics of Behavioral Sciences ........................... 139 Chapter 2. Brain-Behavior Correlations ................................ 145 Chapter 3. Defining the Mind ....................................... 157 Chapter 4. Human Development and Sociocultural Issues ................. 163 Chapter 5. Medical Ethics .......................................... 193 Chapter 6. Psychopathology ........................................ 199 Section VI: U.S. Health Care Chapter 1. u.s. Health Care ......................................... 241 Section VII: Biostatistics and Epidemiology Chapter 1. Biostatistics ............................................. 249 Chapter 2. Epidemiology ........................................... 263 Index .................................................................... 269 ••• VIII KAPLA~. I meulca SEmoN I Embryo ogy Gametogenesis Gametogenesis is the process whereby specialized sex cells (gametes) are produced. Spermatogenesis refers to a series of changes through which spermatogonia differentiate into spermatozoa in the seminiferous tubules of the testes. Oogenesis refers to the series of changes through which oogonia differentiate into oocytes in the ovaries. During gametogenesis, there are changes in DNA content and cellular morphology; these changes are the result of two processes: meiosis and morphologic maturation. During meiosis, the chromosome number and DNA content of the cell are reduced by half, and genetic recombination occurs. During morphologic maturation, the sperm prepares for its motile role, and the egg prepares to support embryologic development. This chapter reviews the processes of meiosis, spermatogeneis, and oogenesis. MEIOSIS A. Gonocyte primordia. The primitive germ cells contain a 2n (diploid) complement of DNA, consisting of 44 autosomes and two sex chromosomes. 1. Before the onset of meiosis, the DNA replicates, and the cell contains twice the normal amount of DNA (4n complement). 2. Each of the 46 chromosomes is present as a pair of chromatids joined together at the centromere. B. First meiotic division 1. During prophase of the first meiotic division, homologous chromosomes pair with each other (synapsis); each homologous pair consists of four chromatids. a. While the homologous chromosomes are paired, there is an interchange of chromatid segments between the two paired chromosomes (crossing over) that leads to genetic recombination. b. In contrast, during mitosis, homologous chromosomes do not pair, and genetic recombination does not occur. 2. The first meiotic division results in a pair of daughter cells, each containing 23 chromosomes (i.e., one member of each homologous pair) but a 2n amount of DNA because each chromosome consists of two chromatids. C. Second meiotic division occurs without prior DNA synthesis. During this process, each of the 23 chromosomes divides at the centromere and gives rise to two haploid (n) daughter cells, each containing 23 chromosomes and a haploid amount of DNA. KULA!._ I meulC8 1 Embryology ) (23,2n) ("P / l! \* "'".v Cell division '! Alignment and , disjunction Centromeres split Gamete Figure 1-1-1. Meiosis. Clini(al Correlate Down syndrome (trisomy 21) is caused by nondisjunction, resulting in three copies of chromosome 21. Common clinical features include mental retardation, short stature, flat nasal bridge, and epicanthal folds. 4 KAPLA~. I meulca D. Nondisjunction refers to an abnormality in either the first or second meiotic division that is characterized by a failure of a homologous pair of chromatids to separate. 1. The result is the production of gametes containing 22 and 24 chromosomes instead of the normal 23. 2. Nondisjunction appears to be a more common abnormality in germ cells of women than in those of men. Gametogenesis SPERMATOGENESIS Spermatogenesis is the process of male gamete formation-from spermatogonia to spermatozoa. A. Primordial germ cells (46 chromosomes, 2n) migrate during embryonic life from the yolk sac wall into the primitive testes, where they become surrounded by the primitive supporting Sertoli cells. B. Spermatogonia and spermatocyte formation 1. Just before puberty, the primordial germ cells (now called gonocytes) differentiate to form the spermatogonia (46 chromosomes, 2n) in the seminiferous tubules of the testes. 2. The spermatogonia divide by mitosis and ultimately give rise to the primary spermatocytes, which undergo meiosis. a. Early in the formation of primary spermatocytes, DNA is replicated; spermatocytes then contain 46 chromosomes and a 4n amount of DNA. b. After a prolonged prophase, spermatocytes complete their first meiotic division, giving rise to a pair of approximately equal-sized secondary spermatocytes (23 chromosomes,2n). C. Spermatid formation. Secondary spermatocytes quickly begin the second meiotic division. 1. Each cell gives rise to two approximately equal-sized spermatids (23 chromosomes, n). 2. Thus, a single primary spermatocyte gives rise to four approximately equal-sized spermatids. D. Spermiogenesis is the process in which the spermatids undergo morphologic differentiation to form spermatozoa. 1. This process includes loss of most of the spermatid cytoplasm, condensation of the nucleus in the sperm head, formation of the acrosome cap over the nucleus, and movement of the centrioles opposite to the acrosomal cap. 2. The spermatozoon consists of a head, neck, and tail. a. The head is formed by the nucleus and is covered by the acrosome and cell membrane. b. The neck contains two centrioles. c. The tail (flagellum) consists of a central axoneme composed of a pair of central microtubules and surrounded by a concentric ring of nine doublets (9 x 2 + 2 arrangement). In a Nutshell The process of spermiogenesis includes loss of most of the cell cytoplasm, condensation of the nucleus to form the sperm head, formation of the acrosome cap over the nucleus, and movement of the centrioles opposite the acrosomal cap. ( 1) Proximally in the middle piece of the tail, the axoneme is surrounded by an inner layer of dense fibers and an outer layer of mitochondria arranged in a circular helix. (2) Distally in the principal piece of the tail, the axoneme is surrounded by dense fibers and an outer fibrous sheath. (3) At the terminal end of the tail, a short end piece consists only of the axoneme covered by the cell membrane. 3. Spermatozoa are released from the Sertoli cells and enter the lumina of the seminiferous tubules. a. Spermatozoa are transported from the testis via the straight tubules, rete testis, and efferent ductules to the duct of the epididymis. This process occurs as a result of the combination of fluid production by the testis, contractile elements in the testes, ciliated cells in the efferent ductules, and smooth muscle in the epididymis. b. Spermatozoa in the epididymis undergo further maturation and acquire their potential for motility and fertilization. KAPLAtf I me illea 5 Embryology In a Nutshell OOGENESIS In males, spermatogenesis does not begin until puberty; in females, oogenesis begins before birth, enters a stage of arrested development until puberty, and is not fully completed unless fertilization occurs. Oogenesis is the process of female gamete formation-from oogonia to oocytes. A. Primordial germ cells. By the fifth week of fetal life, primordial germ cells migrate from the yolk sac wall into the primitive ovaries and contain 46 chromosomes and a diploid amount of DNA. B. Oogonia and oocyte formation l. In the gonad, the primordial germ cells differentiate into oogonia (46 chromosomes, 2n). a. By the end of the first trimester, the oogonia undergo several mitotic divisions in the ovarian cortex. b. After the mitotic divisions, oogonia differentiate to form the primary oocytes. 2. The DNA of the primary oocytes is then replicated, resulting in tetraploid cells (46 chromosomes, 4n). a. The oocytes then begin the prophase of their first meiotic division, which is nearly complete at about the time of birth. Note Prophase I can be further divided into the following stages: preleptotene, leptotene, zygotene, pachytene, diplotene, and diakinesis. b. Instead of continuing on into metaphase, all of the female gametes at birth are primary oocytes arrested in late prophase I of meiosis, and crossing over has already occurred. c. Primary oocytes remain in the diplotene stage of prophase I in primordial follicles until puberty. c. Maturation of primordial follicles 1. At puberty, a few primordial follicles begin to mature during each ovarian cycle, although only one usually fully matures. 2. Once the follicle is mature, the primary oocyte re-enters the first meiotic division, which it completes shortly before ovulation. This division leads to the formation of two unequal cells: the secondary oocyte and the first polar body. a. Although both cells contain an equal number of chromosomes (46) and DNA content (2n), the secondary oocyte receives almost all of the cytoplasm. b. The fate of the first polar body remains uncertain. 3. As soon as the secondary oocyte is formed, it enters the second meiotic division and is released from the ovary during ovulation as soon as it shows spindle formation. a. This division is completed only if fertilization occurs. If fertilization does not occur, the secondary oocyte will begin to degenerate within 12-36 hours after ovulation. b. Division of the secondary oocyte after fertilization produces the second polar body and the ovum (23 chromosomes, n), which contains the female pronucleus and almost all of the cytoplasm from the secondary oocyte. 6 IlPLA!._ I meulC8 Fertilization Fertilization is the fusion of the male and the female gametes. It usually occurs in the widest portion (ampulla) of the uterine tube (oviduct, fallopian tube). Once shed, the ovum is viable for about 24 hours; therefore, the fusion of sperm and egg must occur within 1 day of ovulation for fertilization to occur. Fertilization is a complex process that involves preparatory phases for spermatozoa, which are incapable of fertilization when they arrive in the female tract, entry of the sperm into the egg, and fusion of the male and female genetic material. This chapter reviews the events that lead up to and complete the process of fertilization. CAPACITATION AND ACROSOME REACTION For a spermatozoon to fertilize the ovum, it must undergo capacitation and the acrosome reaction. A. Capacitation is the removal, in the female reproductive tract, of various factors that coat and cover the acrosomal portion of the sperm plasma membrane. B. Acrosome reaction is the process of acrosome enzyme release that occurs when the sper- matozoon binds to the zona pellucida of the female gamete. This reaction is required for the spermatozoon to penetrate the zona pellucida. ENTRY OF THE SPERMATOZOON A. Inhibition of polyspermy. After the entry of one sperm into the zona pellucida and fusion of the sperm and egg cell membranes, important enzymatic events prevent polyspermy (i.e., fertilization by more than one spermatozoon). 1. Cortical reaction. Enzymes that prevent additional spermatozoa from penetrating the oocyte membrane are released from granules in the egg cortex. 2. Zona reaction. Cortical granule enzymes alter the zona pellucida, making the zona impenetrable to additional spermatozoa. B. Continuation of meiosis. Fusion of the sperm and egg cell membranes also induces the resumption of meiosis in the oocyte. 1. The oocyte now completes the second meiotic division, which results in what is called the definitive oocyte as well as the second polar body. 2. The genetic material of the sperm and oocyte are enclosed within structures called the male pronucleus and female pronucleus. meClical 7 Embryology Second meiotic metaphase Figure 1-2-1. Fertilization. FUSION OF THE MALE AND FEMALE PRONUCLEI A. Genetic composition of the pronuclei. The female pronucleus contains 22 + X chromosomes, and the male pronucleus contains either 22 + Y or 22 + X chromosomes. B. Zygote formation. Fusion of the pronuclei to produce the zygote is considered the beginning of embryonic development and entails the following: 1. It restores the diploid number of chromosomes (46) in the zygote. 2. It determines the sex of the embryo. An X-bearing sperm produces an XX (female) individual, whereas a Y-bearing sperm produces an XY (male) individual. 3. It triggers a series of rapid mitotic divisions called cleavage. 8 KAPLAffdme leaI First Week After fertilization and formation of the zygote, designated as day 1 of embryogenesis, the first week is characterized by the mitotic divisions of cleavage, formation of the blastocyst, and implantation. This chapter discusses the events that occur during the first week of zygote development. CLEAVAGE Cleavage is the series of cell divisions that occur as the zygote passes down the uterine tube on its way to the uterus. Cleavage begins within 24 hours of zygote formation. With each division, the daughter cells, called blastomeres, become smaller because these divisions are not accompanied by cell growth. A. Compaction begins with the eight-cell stage. 1. In compaction, the loosely organized blastomeres flatten and are held together by tight junctions. 2. This process also segregates inner blastomeres from outer blastomeres. Inner blastomeres communicate closely via gap junctions. B. Morula. By the third or fourth day, the compacted embryo contains 16-32 cells and is Note Although uterine tube is the Termino/agio Anotamico term, the synonyms oviduct and fallopian tube are commonly used. referred to as the morula. 1. The inner cells of the morula give rise to the inner cell mass. 2. The outer cells give rise to the outer cell mass. BLASTOCYST FORMATION A. Blastocele. Once the morula is inside the uterus, fluid begins to accumulate in the intercellular spaces in the morula and forms a central cavity known as the blastocele. B. Blastocyst (Figure 1-3-0. The zygote, now free of its zona pellucida, is called a blastocyst and consists of two cell groups. 1. The embryoblast (inner cell mass) projects into the cavity. The embryoblast gives rise to the embryo proper. 2. The trophoblast (outer cell mass) forms an outer epithelial layer that surrounds the embryoblast and blastocele. The trophoblast gives rise to the fetal portion of the placenta. KAPUff I me illea 9 Embryology ----- Blastocyst Uterine epithelium Trop h0 bl ast Syncytiotrophoblast { Cytotrophoblast '-\t)'lI---Outer cell mass or trophoblast Figure 1-3-1. Blastocyst at 5 days. IMPLANTATION A. Normal 1. Implantation begins by the end of the first week, when the trophoblast cells over the Clinical Correlate The presence of hCG in urine or serum is a commonly used method for pregnancy testing. embryo blast pole invade the endometrial epithelium of the uterine body. After the embryoblast is embedded within the endometrial stroma, the surface is repaired by a blood clot, which is later replaced by epithelial overgrowth. 2. When the embryo implants, the trophoblast produces human chorionic gonadotropin (heG). This is a hormone that maintains the corpus luteum, and its progesterone secretion until the placenta begins to produce its own progesterone. B. Abnormal 1. The blastocyst may implant in an abnormal site in the uterus near the internal os or cervix. 2. Implantation outside the uterus is referred to as an ectopic pregnancy. Clinical Correlate Due to the narrowness of the uterine tube, ectopic tubal pregnancies that persist beyond the fifth week can rupture the tube. a. Implantation of this type usually results in abortion and severe hemorrhaging during the second month of pregnancy. b. Ectopic sites of implantation occur in the uterine tube (tubal pregnancy), on the surface of the ovary, or in the abdomen, where they often are found in the rectouterine (Douglas) pouch. C. Proliferation of the trophoblast 1. The trophoblast proliferates and differentiates into two cell layers. a. The cytotrophoblast is the single-celled layer adjacent to the embryoblast. b. The syncytiotrophoblast is a thick outer layer that lacks cell boundaries and grows into the endometrial stroma. 2. Excessive growth of the trophoblast may result in proliferation of vesicular masses called hydatidiform moles. Moles secrete hCG and may give rise to benign or malignant tumors. 10 mectical Second Week The second week of development is characterized by continued implantation and expansion of the syncytiotrophoblast until it surrounds the entire embryo and the uteroplacental circulation is established. During this period, the embryoblast splits into two germ layers: the epiblast and hypoblast. The blastocyst cavity is replaced first by the primary yolk sac and then by the secondary yolk sac, and the amniotic and chorionic cavities appear. FORMATION OF BILAMINAR DISC At the beginning of the second week, the cells of the embryoblast begin to differentiate into two layers, the epiblast and hypoblast, forming a bilaminar disc (Figure 1-4-1). A. Epiblast (primary ectoderm) consists of high columnar cells that separate from the cytotrophoblast to form the amniotic cavity. The roof of this cavity is lined by the ectodermal amnioblasts, which are adjacent to the cytotrophoblast. The remaining portion of the epiblast layer lines the floor of the cavity. During the third week, the epiblast gives rise to two germ layers: the embryonic ectoderm and mesoderm. B. Hypoblast (primary endoderm) consists of low cuboidal cells adjacent to the blastocyst cavity. This layer contributes to the lining of the primary yolk sac. TROPHOBLAST DEVELOPMENT A. Extraembryonic mesoderm 1. On days 11 and 12, the trophoblast gives rise to the extraembryonic mesoderm, which is loosely arranged around the amnion and primitive yolk sac. KAPLAff I medlea 11 Embryology Cytotrophoblast Syncytiotrophoblast Enlarged blood vessels (sinusiods) ~~~~~~~;:(~.~. Amnioblasts I piblast S·,I ammar . . Hypoblast em. bryonic ~!':SI;':~JirJ:·.:;~";·~~·.:: ; (embryonic disk . ~ntoderm) Amniotic cavity Figure 1-4-1. Blastocyst at 10 days. 2. Cavities within the extraembryonic mesoderm quickly fuse to form the extraembryonic coelom. The coelom divides the mesoderm into the extraembryonic somatic mesoderm, which covers the cytotrophoblast and amnion, and the extraembryonic splanchnic mesoderm, which covers the yolk sac. B. Uteroplacental circulation 1. The trophoblast and extraembryonic somatic mesoderm lining comprise the chorion. 2. Trophoblastic erosion of maternal blood vessels allows blood to flow from sinusoids (enlarged, congested capillaries of the endometrium) into the lacunar or intervillous spaces that have formed in the embryonic syncytiotrophoblast. When this occurs, the primitive uteroplacental circulation is established. C. Chorionic cavity 1. The expanded extraembryonic coelom forms the chorionic cavity on day 13. 2. The bilaminar embryo, amnion, and yolk sac are suspended in this cavity by the connecting stalk, which is a condensation of extraembryonic mesoderm that later develops into the umbilical cord. 3. At this time, the secondary (definitive) yolk sac is pinched off from the primary yolk sac (Figure 1-4-2). 12 iiieclical Second Week Lacunar network Amniotic cavity Extraembryonic somatic mesoderm --===:;li.W-AlEi(;li? ~~~~_ Secondary yolk sac Chorion--------~~~~~·) of primitive yolk sac 'R,... mn~l"lt Figure 1-4-2. Blastocyst at 14 days. D. Decidual reaction. During week 2 of development, cells of the decidua, the functional layer of the pregnant endometrium, respond to implantation and progesterone secretion by enlarging and accumulating glycogen and lipid. The entire tissue becomes edematous. This response is known as the decidual reaction. UPLA~. I meulca 13 Third Week The third week of development is characterized by the formation of all three germ layers during the process known as gastrulation. Thus, the bilaminar disc is converted into the triiaminar disc. It is during this period that the cephalocaudal, left-to-right, and anteroposterior axes of the body are established. In addition, the notochord develops, the allantois appears as a posterior diverticulum of the yolk sac, and the trophoblast expands rapidly to form a complex set of villi that ensure the exchange of gases and nutrients between maternal and embryonic tissues. FORMATION OF TRILAMINAR DISC A. Primitive streak 1. During the third week of development, the cephalocaudal axis of the embryo becomes defined by the primitive streak, which is a linear thickening of the ectoderm cells on the caudal part of the dorsal embryonic disc. The streak is delimited rostrally by the primitivenode. 2. The epiblast cells of the primitive streak proliferate and migrate inward (invagination) between the epiblast and hypoblast layers. Initially, they replace the original hypoblast with the definitive endoderm. Migrating epiblast cells then form a third germ layer, the intraembryonic mesoderm. The remaining epiblast cells are the ectoderm. Thus, the three definitive germ layers are derived from the epiblast. B. Intraembryonic mesoderm 1. Mesodermal cells form a loosely arranged tissue known as mesenchyme. The lateral extension of mesoderm establishes direct contact with the extraembryonic mesoderm that covers the yolk sac and amnion. 2. Ectodermal and endodermallayers fuse at the cephalic and caudal ends of the embryonic disc to form the buccopharyngeal and cloacal membranes, respectively (Figure 1-5-1). Migrating mesodermal cells do not penetrate these areas but pass on either side to surround them. Rostral to the buccopharyngeal membrane, the mesoderm forms the cardiogenic plate that will give rise to the heart. I KAPLArf medlea 15 Embryology Amniotic ectoderm Embryonic ectoderm Hensen node (primitive knot) Notochord Cephalic end Intraembryonic mesoderm Cloacal membrane Figure 1-5-1. Longitudinal section of embryo at 17 days. C. Fate of the primitive streak. The primitive streak usually degenerates and disappears. However) in abnormal cases, some remaining multipotent ceJls of the streak may give rise to sacrococcygeal teratomas, which are tumors of many cell types, found on or near the midline. More common in females than in males, these tumors may become malignant. FORMATION OF NOTOCHORD A. Day 16. About this time, cells of the primitive streak migrate rostrally and form the tube-like notochordal process. B. Day 17. By this time, the mesoderm layer and notochordal process (a mesodermal deriva- tive) separate the ectoderm and endoderm layers entirely, with the exception of the buccopharyngeal and cloacal membranes. C. Day 18. By this time, disintegration of the floor of the notochordal process and the fused underlying endoderm opens a transient passage, the neurenteric canal, which connects the yolk sac cavity and the amniotic cavity. FORMATION OF ALLANTOIS On about day 16, the allantois forms as a diverticulum of the posterior wall of the yolk sac, which extends into the connecting stalk. Both the allantois and the yolk sac are responsible for early blood formation, which previously took place extraembryonically. At the beginning of the third week, angioblasts in the visceral mesoderm of the yolk sac wall form clusters and cords that become canalized. Centrally located cells give rise to primitive blood cells and cells on the periphery flatten to form endothelial cells that line blood islands. 16 ii1.Ctical Third Week TROPHOBLAST DEVELOPMENT The chorion differentiates to form chorionic villi during the third week of development (Figure 1-5-2). A. Primary villi are formed when cords of cytotrophoblast cells migrate into the irregular processes of the syncytial layer. B. Secondary villi are formed when the extraembryonic mesoderm of the chorion invades the cytotrophoblastic core of the primary villi. C. Tertiary villi are formed by organization of the core mesoderm into capillaries. These cap- illaries make contact with vessels of the connecting stalk and chorion, which, in turn, make contact with the intraembryonic circulatory system to connect the placenta to the embryo. Cytotrophoblast core " " Extraembryonic somatic mesoderm ",:. :" '.>'- ". Primary villous Maternal blood Chorionic cavity Trophoblastic lacunar (intervillous) network Figure 1-5-2. Diagram of trophoblast with embryo (left) and longitudinal section of villus (right) during the third week. UPLllf I me d1C8 17 Fourth to Eighth Weeks Beginning approximately in the third week and extending through the eighth week is the interval known as the embryonic period. This period of embryogenesis and organogenesis is characterized by the cephalocaudal and lateral folding that transforms the embryonic disc into a tube and by the formation of the organs and systems of the body from derivatives of the three germ layers. At the end of this period, major external body features are recognizable. The subsequent interval from the beginning of the third month until parturition is known as the fetal period, a period of organ system maturation and body growth. This chapter reviews the processes that occur during the embryonic period. ECTODERMAL DERIVATIVES A. Central nervous system (CNS) (Figure 1-6-1) 1. Neural plate. At the cephalic region of the embryo, the notochord induces a thickening of ectoderm, which becomes the neural plate. The neural plate increases in length as the primitive node and primitive streak move caudally. 2. Neural groove and neural crest. Invagination of the neural plate by day 18 results in the formation of the neural groove. The lateral edges of the plate form neural folds, which join in the midline as the neural groove deepens. The edge of each fold is known as the neural crest. 3. Neural tube. The neural tube is formed as the neural folds fuse in the midline. Fusion begins in the region of the future neck (fourth somite) and proceeds in cephalic and caudal directions. upurr I meillea 19 Embryology Neural plate Neural told Notochordal process Ectoderm Neural told ~V~ ~~:::::~ A -- Neural groove Day 18 Neural told Rostral neuropore B --- Neural crest In a Nutshell Caudal neuropore (closes at 27 days) Ectodermal Derivatives • Nervous system • Otic and lens placode • Pituitary and mammary glands Ectodermal Neural Crest Derivatives • Dorsal root ganglia • Sensory ganglia of cranial nerves • Autonomic ganglia Neural crest Failure to close results in ancephaly, causing polyhydraminos and increased alpha-teto protein. C --- • Skin, hair, nails, tooth enamel Neural tube Day 22 Failure to close results in spina bitida Alphateto protein. Figure 1-6-1. Neural tube development (cross-section). 4. Brain and spinal cord. The cephalic end of the neural tube eventually dilates to form the forebrain, midbrain, and hindbrain. The spinal cord is formed from the remainder of the tube. Neural crest cells form the dorsal root ganglia, sensory ganglia of the cranial nerves, autonomic ganglia, meninges, Schwann cells, adrenal medullary cells, melanocytes, and ectomesenchyme of the head and neck. B. Otic placode and lens placode. Subsequent to neural tube closure, two additional ectoder- mal thickenings, the otic placode and the lens placode, appear in the cephalic region of the embryo. 1. The otic placode invaginates to form the otic vesicle, which gives rise to the organs of • Meninges • Schwann cells • Adrenal medulla • Melanocytes 20 meilical hearing and equilibrium. 2. The lens placode invaginates to form the lens vesicle, which forms the lens during the fifth week of development. c. Other ectodermal derivatives include skin, hair, nails, subcutaneous glands, mammary glands, pituitary gland, and tooth enamel.