SEXUAL DEVELOPMENT GAMETOGENESIS EMBRYOLOGY Cellular mechanisms She arrived

SEXUAL DEVELOPMENT GAMETOGENESIS EMBRYOLOGY: Cellular mechanisms She arrived by default. He was miffed. : : Am I going dotty, or what? German Umlaut to modify a vowel French trema to indicate emphasis : Paraoophoron Zoological : : naive : : : MULLERIAN DUCT English diaeresis - to show second ‘o’ is pronounced independently

SEXUAL DEVELOPMENT OVARY UTERINE TUBE VAGINA UTERUS : VULVA MULLERIAN DUCT GONAD on hold WOLFFIAN DUCT TESTIS PARAMESONEPHRIC DUCT and UROGENITAL SINUS & MESONEPHRIC DUCT TUBERCLE INTERSTITIAL CELLS RETE EPIDIDYMIS TESTIS PROSTATE PENIS urethra DUCTUS TUBULUS DEFERNS RECTUS EFFERENT SEMINIFEROUS DUCT SEMINAL TUBULE VESICLE BULBOURETHRA L GLAND

Default pathway GONAD on hold Y OR GONAD on hold OVARY no Y Sex-determining Factor/SRY acts on gonad TESTIS Driven pathway Testosterone TESTIS INTERSTITIAL CELLS act on Repro ducts : TUBULUS RECTUS SEMINIFEROUS TUBULE UROGENITAL SINUS & TUBERCLE MULLERIAN DUCT Para. Meso. N Mullerian-inhibiting Factor SERTOLI CELL WOLFFIAN DUCT

Default pathway GONAD on hold : WOLFFIAN DUCT regresses OVARY MULLERIAN DUCT GENITAL TUBERCLE etc OVARY ? UTERINE TUBE UTERUS VAGINA VULVA

Mesonephric REMNANTS IN THE WOMAN MULLERIAN DUCT OVARY : UTERINE TUBE VAGINA : Epoophoron & Paraoophoron UTERUS VULVA : Gartner’s cyst WOLFFIAN DUCT regresses, except for

infifferent GONAD MALE FACTORS & TARGETS IN SEXUAL DEVELOPMENT Y Sex-determining Factor/SRY UROGENITAL SINUS & TUBERCLE Dihydrotestosterone TESTIS INTERSTITIAL CELLS WOLFFIAN DUCT Testosterone TUBULUS RECTUS SEMINIFEROUS : TUBULE SERTOLI CELL Driven pathways : Mullerian-inhibiting Factor MULLERIAN DUCT regresses

GONAD on Y hold DRIVEN PATHWAYS Mullerianinhibiting Factor Sex-determining Factor/SRY MIF TESTIS MULLERIAN DUCT regresses Testosterone Dihydrotestosterone WOLFFIAN DUCT INTERSTITIAL CELLS RETE EPIDIDYMIS TESTIS UROGENITAL SINUS &TUBERCLE PROSTATE PENIS urethra DUCTUS DEFERNS TUBULUS RECTUS EFFERENT SEMINIFEROUS DUCT SEMINAL TUBULE VESICLE BULBOURETHRAL GLAND

Paramesonephric REMNANTS IN THE MAN WOLFFIAN DUCT TESTIS INTERSTITIAL CELLS RETE EPIDIDYMIS TESTIS UROGENITAL SINUS &TUBERCLE PROSTATE PENIS urethra DUCTUS DEFERNS TUBULUS RECTUS EFFERENT SEMINIFEROUS DUCT SEMINAL TUBULE VESICLE : Appendix testis MULLERIAN DUCT regresses, except for BULBOURETHRAL GLAND Prostatic Utricle

VERY LUCKY PROSTATE SECTION FIBROUS STROMA URETHRA PROSTATE Ejaculatory duct P R O S T A T I C Prostatic URETHRA UTRICLE ED GLANDS ED VERUMONTANUM or Seminal colliculus - the ridge in the floor of the prostatic urethra

SOME SEXUAL HOMOLOGUES OVARY UTERINE TUBE VAGINA UTERUS Ovary : VULVA Uterine tube Gartner’s duct Efferent ducts Appendix testis Epididymis P Utricle : Epoophoron Testis TESTIS INTERSTITIAL CELLS RETE EPIDIDYMIS TESTIS Uterus Clitoris Penis Scrotum PROSTATE PENIS urethra DUCTUS TUBULUS DEFERNS RECTUS EFFERENT SEMINIFEROUS DUCT SEMINAL TUBULE VESICLE Labia majora BULBOURETHRA L GLAND

Problems of sexual development can arise at several points, thus: (i) Absent or faulty SRY gene in the male (ii) Failure of testis cells to respond to the gene's product : (iii) Absent or defective MIF gene; or problems in the Mullerian duct's response to MIF (iv) Leydig-cell failure to make and deploy the enzymes to produce testosterone (v) Defective or absent androgen receptor in the Wolffianduct and external-genital targets for testosterone ( XY genotype, but woman’s phenotype)

Problems of sexual development can arise at several points, thus: (ii) Failure of testis cells to respond to the gene's product GONAD on hold (iv) Leydig-cell failure to make and deploy the enzymes to produce testosterone Y (i) Absent or faulty SRY gene in the male Sex-determining Factor/SRY MIF TESTIS MULLERIAN DUCT regresses Testosterone WOLFFIAN DUCT TESTIS Mullerianinhibiting Factor INTERSTITIAL CELLS RETE EPIDIDYMIS TESTIS Dihydrotestosterone UROGENITAL SINUS &TUBERCLE PROSTATE PENIS urethra DUCTUS TUBULUS DEFERNS RECTUS EFFERENT SEMINIFEROUS DUCT SEMINAL TUBULE VESICLE (iii) Absent or defective MIF gene; or problems in the Mullerian duct's response to MIF BULBOURETHRA L GLAND (v) Defective or absent androgen receptor in the Wolffian-duct and external-genital targets for testosterone ( XY genotype, but woman’s phenotype)

Epiphenomenon Something happening along with something else, and perhaps related to it “An attendant phenomenon appearing with something else and referred to that as its cause” - Webster’s Collegiate Dictionary 5 th ed 1948

MA & PA MEIOSIS AIM: From one 1 o spermatocyte to produce four spermatids, each with: (i) 23 chromosomes (haploid #); (ii) each chromosome derived from either Ma or Pa; (iii) but with bits of Pa’s chromosome replacing some of Ma’s, and vice versa Think quartering cuts M P { M { X 23 P M P

MA & PA MEIOSIS { M M PP P DNA synthesis 3 maternal-paternal homologue pairing 3 M { P { { Primary spermatocytes M 3 3 Each chromosome now a pair of chromatids held together by a centromere maternal & paternal #3 chromosomes Bivalent for crossing over of aligned chromatids { DNA excison & ligation { P Maternal 3 { M FOUR SPERMATIDS Meiotic division I Paternal 3 Maternal 3 { { @ Meiotic division II Paternal 3 Centromere splitting Paternal 3 Secondary spermatocytes Maternal 3

MA & PA MEIOSIS { M M { M PP P DNA synthesis 3 3 maternal & paternal #3 chromosomes Each chromosome now a pair of chromatids held together by a centromere { { P { M maternal-paternal homologue pairing

Primary spermatocytes @ { P { M M { P { DNA excision & ligation Bivalent for crossing over of aligned chromatids Meiotic division I Maternal 3 { { Paternal 3 Secondary spermatocytes @ Site of trouble DNA exchange disrupts or cuts out genes

Meiotic division I Maternal 3 { { Paternal 3 Meiotic division I Secondary spermatocytes Random assignment of maternal & paternal chromosomes (disjunction)*, e. g. , 1 2 3 4 5 6 Paternal Maternal Paternal Maternal etc 1 2 3 4 5 6 Maternal Paternal Maternal Paternal etc * Site of trouble Wrong assignment of chromosomes, e. g. , 2 #21 s to one 2 o spermatocyte & none to the other. Then + one from oocyte = Trisomy 21 in the zygote

Meiotic division II Secondary spermatocytes FOUR SPERMATIDS Paternal 3 Maternal 3 { { Maternal 3 Meiotic division II Maternal 3 Centromere splitting Paternal 3 Chromatids now chromosomes

MA & PA MEIOSIS { PP P DNA synthesis 3 3 maternal-paternal homologue pairing M { { { M M Primary spermatocytes M P 3 3 Bivalent for crossing over of aligned chromatids Each chromosome now a maternal & paternal pair of chromatids held #3 chromosomes together by a centromere { { P FOUR SPERMATIDS Meiotic division I Paternal 3 Maternal 3 { { Maternal 3 { M DNA excison & ligation @ Meiotic division II Paternal 3 Centromere splitting Paternal 3 Secondary spermatocytes Maternal 3

OOCYTE’S MEIOSIS RESULTS OOCYTE Maternal 3 Paternal 3 OR Maternal 3 Paternal 3 Zp 2 nd POLAR BODY 1 st POLAR BODY unity function disjunction disunity dysfunction nondisjunction

OVARY SLIDES Many of our animal slides have several pale glandular masses - corpora lutea - that have pushed almost all the follicles to a part of the ovary not in the section. There are sometimes quite a few primordial (& a few primary and later) follicles, but the oocytes are shrunken & distorted. Sections through antral follicles can miss the oocyte; or hit the oocyte, but miss the nucleus Describe the ovarian follicle in terms of how far the follicular/ granulosa cells have progressed: squamous, cuboidal, small & round; one layer, two layers, multilayered; formed an antrum, or not yet; made a very large antrum, etc. The large corpus albicans will not be in these small-animal ovaries

WHERE AM I? Online Anatomy Module 1 INTRO & TERMS CELL EPITHELIUM CONNECTIVE TISSUE MUSCLE NERVOUS SYSTEM AXIAL SKELETON APPENDICULAR SKELETON MUSCLES EMBRYOLOGY C Cellular mechanisms & Malformations

The Approach W Beresford To present what cells do, via particular proteins, to create an embryo - cellular mechanisms Cells assemble as tissues, which can have their own collective tissue actions & interactions These cellular & tissue events can fail for a multitude of reasons: we can examine and classify the resulting malformations & defects Orofacial development offers examples 101 Embryology. FM. ppt We can try to break down the underlying reasons why cells misbehave so, & when vulnerability is greatest As one aspect, one can list known agents of teratogenesis - the causing of a malformations

Some agents of teratology Vitamin A & Retinoids Thalidomide X-rays & Radiation Cancer chemotherapy agents Cortisone Sex steroids Rubella virus Folic-acid & other deficiencies Ethyl alcohol A clear subtext: avoid these when pregnant, or possibly so

Teratology & Genetic defects: General comments 1 To function, we have thousands of protein types, which are coded for by individual genes, shared out amongst the chromosomes Defective genes - altered, missing or misplaced parts, or on extra chromosomes , etc - result in proteins that are absent, altered, or with missing (critical? ) parts Such bad-protein problems may prevent the embryo from living - lethal mutations & lethal losses Other bad proteins permit development, but the individual has minor or major impairment to her/his metabolism - lactose intolerance vs phenylketonuria Other bad proteins disturb development so that the baby is born with anatomical defects involving tissues, limbs, organs, systems - these are the substance of Teratology The whole sorry story is medical genetics

Teratology & Genetic defects: General comments 2 The many defects in both metabolism and anatomical structure may show up in combinations, whose patterns have sometimes long been noticed & named as So-&-so’s syndrome Every month, in journals such as Development & Mechanisms of Development, researchers report having stopped a particular protein from working in mice (e. g. , bad-protein prevent the picture embryo by. Such knockouts) with problems a resultingmay developmental from living - lethal mutations & losses closely matching one of the many human syndromes Knowing what the protein does - signals, receives signals, is a structural component (e. g. , of cartilage or bone matrix), etc offers a molecular explanation for the disorder, but showing how the common agents of teratogenesis act has not gone quite as well And the ‘explaining’ has to extend to events at the cell & tissue levels, as follow here

Teratology & Genetic defects: General comments 3 Development takes place over many months, and some organs need much more time than others: for instance, the nervous system is not even finished at birth This creates a long period of vulnerability for some systems - e. g. , face, eyes, teeth, genitalia, & brain. [Thus, many agents & factors cause mental retardation. ] Some processes are more vulnerable to disruption than others, creating critical periods while a particular process is under way The early formation of the body plan and ‘starting’ the various organs make the embryonic period (first two months) more critical than the ‘growing’ fetal period Conversely, some processes occur later, so that certain agents can only act then , e. g. , excess male steroid hormone masculinizing female external organs

Cell behaviors underlying embryogenesis I Cell signaling Cell division Stem-cell renewal Cell differentiation Cell polarization Cell adhesion Cell migration Apoptosis - Cell death Differential growth Mesenchymal-epithelial conversion Digestion of ECM Tissue fusion Epithelio-mesenchymal transformation Branching morphogenesis Tissue perforation Canalization Tissue-to-tissue signaling Symmetric & asymmetric divisions Defects in these cellular processes are part of the basis for malformations of the embryo

Cell behaviors underlying embryogenesis II Cell division rapidly increases the number of cells & the activties that they undertake First round of division Second round of division Third round of division, & so on Cell differentiation Unspecialized cell becomes committed to, or determined for, a particular fate, e. g. , smooth muscle At some stage, the precursor cells stop dividing

Cell behaviors underlying embryogenesis III Continuity of cell differentiation Although one can define stages, by the cell’s appearance, contents (e. g. , new proteins) & behavior, the process is far more continuous than the naming of stages suggests Stem cells If all the starting cells became differentiated, and these were then RENEWAL lost, there could be no replacement. Stem cells solve this problem: (i) by Stem cells being able to turn into specialized cell kinds, but (ii) by also being able to replace/renew themselves DIFFERENTIATION

Cell behaviors underlying embryogenesis IV Symmetric & asymmetric divisions These divisions produce identical offspring This division yields differing cells - asymmetric division

Cell behaviors underlying embryogenesis V Mitotic cleavage plane can affect cell destiny Cell polarization Apical/upper surface Lateral/side surface Basal/bottomsurface The cell reacts to its neighbors and other influences to acquire a special shape, different surfaces, & exact placement of its contents

Cell behaviors underlying embryogenesis VI Cell polarization takes various forms A muscle cell is polarized in relation to a contractile axis or direction A migrating cell is polarized in relation to the substrate that it is crawling on, and the direction in which it is going LUMEN Epithelial cells are polarized in relation to their basal lamina, the lumen, & each other BL

Cell behaviors underlying embryogenesis VII Cell adhesion takes various forms Muscle cells attach to each other to synchronise contraction & transmit force A migrating cell adheres to, pulls on, & releases from its substrate LUMEN Epithelial cells attach to their basal lamina, & to each other, by a variety of junctions BL Divorce comes easily: adhesions are made to be broken

Cell behaviors underlying embryogenesis VIII Epithelio-mesenchymal transformation/transition BL usually prior to migration by the converted cell

Cell behaviors underlying embryogenesis IX Mesenchymal-epithelial conversion BL Occurs normally when: mesoderm cells form the somites mesenchymal cells become endothelium to line the heart & vessels intermediate mesodermal cells form the kidney tubules & glomerular epithelia

Cell behaviors underlying embryogenesis X Cell migration A migrating cell adheres to, pulls on, & releases from its substrate. Requires: Attachment to a substrate/floor Release of attachment & reattachment Actin filaments, soluble actin, & actin-minders, to move Mitochondria & energy sources Signals for direction, speed, etc

Cell behaviors underlying embryogenesis XI Apoptosis - Cell death followed by discreet removal of the dead cell by macrophages Digestion of ECM Digestion of the basal lamina BL Remodeling of connective tissue ECM

Cell behaviors underlying embryogenesis XII You’ve seen one result Apoptosis - Cell death Digestion of ECM Both processes are involved in the loss of the tadpole’s tail at metamorphosis into a froglet

Cell behaviors underlying embryogenesis XIII Thus far, we’ve looked at one or two cells, but as cells multiply they create tissues that act as larger units which can shape, fuse, interact, etc Differential growth Local growth of Mesenchyme & epithelium produces a bulge Growth slower here Bulges are a frequent feature of development

Cell behaviors underlying embryogenesis XIV Differential growth Local growth of Mesenchyme & epithelium produces a bulge Growth slower here Although here it looks as though mesenchyme is driving the excessive growth, both tissues are collaborating & growing, and ectoderm & endoderm elsewhere can be the major players, e. g. , in the formation of the nervous system & liver respectively

EXTERNAL/INTERNAL EMBRYO: CNS I 35 days pc 3 brain ‘vesicles’ are subdividing Mesencephalon Rhombencephalon BRAIN Diencephalon now four; then Rhombencephalon divides into Met- & Myel-encephalons Cephalic flexure/bend Cervical flexure start the folding Telencephalon Brain ectoderm by differential growth has produced brain vesicles, the cord, and two major curvatures SPINAL CORD

Cell behaviors underlying embryogenesis XV Tissue-to-tissue signaling Have the notochord signal the overlying ectoderm to take on extra functions by making a separate tubular structure - the NEURAL TUBE and the NEURAL CREST NC N C MESODERM Reciprocal Mesenchymal-epithelial signaling is very widely used

Cell behaviors underlying embryogenesis XVI Fusion of processes I Initially an epithelial fusion Growth

Cell behaviors underlying embryogenesis XVII Fusion of processes II Initially an epithelial fusion but followed by: some cell death breakdown of basal lamina ingrowth of mesenchyme some epithelial conversion to mesenchymal cells

Cell behaviors underlying embryogenesis XVIII Fusion of processes III Reconstruction of the line of fusion almost complete

Cell behaviors underlying embryogenesis XIX Septation - creation of a partition/septum I Epithelial proliferation Remodeling of basal lamina Growth of mesenchyme Epithelial fusion Epithelial proliferation Remodeling of basal lamina Growth of mesenchyme Mesenchymal breakthrough

Cell behaviors underlying embryogenesis XX Septation - creation of a partition/septum II Epithelial fusion

Cell behaviors underlying embryogenesis XXII Septation - creation of a partition/septum III Two Mesenchymal breakthrough compartments

Cell behaviors underlying embryogenesis XXIII Septation - creation of a partition/septum IV One compartment In practice, septation is often achieved by having ingrowth proceed from both sides of the compartment to be divided

Septation produces lung alveoli >90% of lung alveoli are created by septation after birth, so this embryonic process is kept running post-natally One compartment becomes two, but not completely separated

Cell behaviors underlying embryogenesis XXIV Membrane perforation Cell apoptosis BL dissolution & remodeling

Branching morphogenesis I Cell behaviors underlying embryogenesis XXV Epithelio-mesenchymal interactions result in side buds that grow, then duplicate again, & again Eventually producing final working units, such as lung alveoli or gland secretory units

Branching morphogenesis II Eventually producing final working units, such as lung alveoli or gland secretory units by: Construction of lumens Differentiation into duct & secretory cells Construction of stromal elements & vessels from mesenchyme Innervation from ANS Stroma [ However, the simple alveolar gland shown will NOT require the branching morphogenesis needed for compound glands & the lungs ]

Branching morphogenesis III Selective cell proliferation & cell polarization to change the direction of growth Remodeling of basal lamina Branch point Epithelial proliferation inhibited ECM firmed up Digestion of mesenchyme

Branching morphogenesis IV It gets interesting after just four generations of branching The amount of growth before the change of direction is clearly critical to making a compact organ

Canalization Cell behaviors underlying embryogenesis XXVI Outgrowth of cells to produce a cord Differentiation into duct/vessel-lining cells Apoptosis & separation to hollow out the cord Endothelial-cell cords can anastomose (join end-to-end) to create a capillary network

Vessel construction Endothelial-cell cords can anastomose (join end-to-end) to create a capillary network Or surrounding mesenchymal cells can build the connectivetissue and muscle layers of a larger vessel’s wall ADVENTITIA INTIMA MEDIA

Ligamentous conversion Cell behaviors underlying embryogenesis XXVII Almost the opposite of canalization is the taking of a fetal vessel (or a duct) out of use by converting it to a fibrous cord or ligament Death of endothelial & muscle cells Reinforcement of adventitial connective tissue LIGAMENT E. g. , Ligamentum teres of the liver was the left umbilical vein

OROFACIAL MALFORMATIONS : Processes DYSPLASIA wrong growth HYPOPLASIA too little growth HYPERPLASIA too much growth FUSION FAILURE SEPARATION FAILURE PERSISTING PAST TIME CYST FORMATION

Basis for malformations: Hypoplasia Too little growth Failure to grow fully or at all Instead of

Basis for malformations: Failure to fuse Growth One reason for no fusion Hypoplasia of one/both processes means that they do not meet, and therefore they cannot fuse Adhesion problems could be another reason

CLEFT PALATE from HYPOPLASIA of MAXILLARY PROCESS FACE

FACIAL DEFECTS: Failures of processes to fuse OBLIQUE FACIAL CLEFT Maxillary & Nasolateral MEDIAN CLEFT LIP Nasomedial & Nasomedial MEDIAN CLEFT JAW Mandibular & Mandibular UNILATERAL CLEFT LIP Maxillary & Nasomedial UNILATERAL MACROSTOMIA Mandibular & Maxillary FACE

PALATAL DEFECTS II: Failures to fuse COMPLETE UNILATERAL ANTERIOR CLEFT Palate & Lip Primary & Lateral palatines AND Maxillary & Nasomedial POSTERIOR CLEFT PALATE Complete Can occur independently; can be partial; anterior cleft can be bilateral PALATE

Factors causing cleft lip/palate (failed fusion) Trisomy 13 Vitamin A & Retinoids Quite common - affect about 1 in 1000 births Anticonvulsants Cortisone? Fusion of processes II Initially an epithelial fusion but followed by: some cell death breakdown of basal lamina ingrowth of mesenchyme some epithelial conversion to mesenchymal cells

TONGUE MALFORMATIONS I ARCH LATERAL LINGUAL SWELLINGS Failure of these to fuse properly causes a DEEP MEDIAL SULCUS or at worst a BIFID TONGUE I II IV Overgrowth MACROGLOSSIA Undergrowth MICROGLOSSIA “Anatomist! He speak with forked tongue. ”

TONGUE MALFORMATIONS II Remnant of duct epithelium forms a LINGUAL CYST FORAMEN CECUM from whence thyroglossal duct set out to create thyroid gland Part of duct opens back to foramen “FISTULA” TONGUE

OROFACIAL MALFORMATIONS II Sources BRAIN I II MECKEL’S SYNDROME & FRONTO-NASAL DYSPLASIA Defects from bad brainfrontonasal process interactions PIERRE-ROBIN SYNDROME & TREACHER-COLLINS SYNDROME Include poor neural crest migration & behavior Defects from first branchial arch development

Basis for malformations: Failure to migrate One of many neural-crest instances SACRAL N T Neural crest cells did not migrate to the colon to become the parasympathetic neurons Result - Parasympathetic ganglion neurons absent Condition an enlarged paralyzed colon - Hirsprung’s congenital aganglionic megacolon Symptom - Newborn’s total constipation

Basis for malformations: Failure to perforate Membrane persists Processes blocked or not started Cell apoptosis BL dissolution & remodeling The earlier intrusion of mesenchyme can do this

Failure to perforate Imperforate anus/Anal atresia Endodermal tube has started many organs ESOPHAGUS TRACHEA& BRONCHI (& lungs) STOMACH LIVER INTESTINES PANCREAS If this cloacal membrane persists, later the rectum will lack an opening Creating a hole surgically is easy; ensuring good sphincter CLOACA action may not be.

Basis for malformations: Apoptotic failure Apoptosis - Cell death Both processes are involved in the loss of the tadpole’s tail Digestion of ECM “& it happened to your tail. ” Apoptotic failure Occasionally, humans have a persisting tail LIVER INTESTINES Or webs between the fingers “Join the Navy, perhaps? ”

Basis for malformations: Septation failure Absent or Incomplete Septation Lung alveoli insufficiently partioned One compartment stays Heart ventricles stay connected Semilunar valves not formed, etc

Embryology XII How do the brain & cord form? How do the brain & cord come to be enclosed in soft wrappings and bone? Is the enclosure sometimes not complete? Yes - another, but not so rare, malformation Spinal canal open Cord exposed

Neural Plate Events in neural tube formation Ectodermal Thickening Neural Groove Downgrowth Clefting or Trough production Ingrowth Fusion Neural Tube Separation Tube production

Many agents of teratology affect the neural tube Folic-acid & folic acid antagonists X-rays & Radiation OPEN Ethyl alcohol Vitamin A & Retinoids CLOSED OPEN The open ends are the Neuropores Failure of the neuropores to close & create a closed fluid-filled system causes severe CNS defects Often compounded by a lack of enclosure by the meninges and spinal/cranial bone

‘SPINA BIFIDA’ varies in severity BRAIN HEART The spinal tube has failed to close & get established - a very severe defect, leaking CSF & causing secondary brain abnormalities Spinal canal open - bifid 25 d pc Several names are used to indicate the ‘openess’ of the cranial bone/spine, & how protruding or open are the meninges Cord formed properly, but exposed

Monozygotic twins A felicitous, if expensive, malformation is twinning Except for placental arrangements, each twin’s development is normal How is it that I have an identical twin? Bill Ben BLASTOCYST INNER CELL MASS SPLITS INTO TWO The common event

Conjoined/Siamese twins (Monozygotic) A rare, unhappy outcome A malformation Why are we stuck together? Bill Ben BLASTOCYST This depicts a relatively benign chest connection INNER CELL MASS did not separate completely

Malformations in particular systems BRAIN HEART 25 d pc For particular organs - heart, brain, lung, eye, etc - their complicated development can go astray in many ways. Some of these events are very rare and are of more interest for theory than practice; others, for instance in the heart & genitourinary systems, are not that uncommon, and need to be understood and learned

WHERE AM I? Online Anatomy Module 1 INTRO & TERMS CELL EPITHELIUM CONNECTIVE TISSUE You are at the End Caution how you exit. BACK on your browser is needed Unfortunately there is no way that you can NERVOUS SYSTEM directly reach other topics listed here by AXIAL SKELETON clicking on them. You APPENDICULAR SKELETON get there by going back MUSCLES to the Paramedical Anatomy menu MUSCLE EMBRYOLOGY C

EXTERNAL EMBRYO II 25 days pc BRAIN Anterior NEUROPORE Tube not fully closed as brain at a very early stage BRANCHIAL/PHARYNGEAL ARCHES starting for face & neck structures CARDIAC BULGE SOMITES BODY STALK Posterior NEUROPORE bulging under the ectoderm

EXTERNAL EMBRYO III 35 days pc LENS PLACODE for eye LIMB BUD UMBILICAL CORD CARDIAC SWELLING SOMITES bulging under the ectoderm TAIL part for coccyx; part for discard LIMB BUD