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Table of Contents
                            Larsen's Human Embryology
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Chapter 1
	1 - Gametogenesis, Fertilization, and First Week
		Primordial Germ Cells
			Primordial Germ Cells Reside in Yolk Sac
			Primordial Germ Cells Migrate into Dorsal Body Wall
			Primordial Germ Cells Stimulate Formation of Gonads
			Timing of Gametogenesis is Different in Males and Females
			Meiosis Halves Number of Chromosomes and DNA Strands in Sex Cells
				First Meiotic Division: DNA Replication and Recombination, Yielding Two Haploid, 2N Daughter Cells
				Second Meiotic Division: Double-Stranded Chromosomes Divide, Yielding Four Haploid, 1N Daughter Cells
			Male Germ Cells Are Translocated to Seminiferous Tubule Lumen during Spermatogenesis
			Sertoli Cells are Also Instrumental in Spermiogenesis
			Continual Waves of Spermatogenesis Occur throughout Seminiferous Epithelium
			Spermatozoa Undergo Terminal Step of Functional Maturation Called Capacitation
			Primary Oocytes Form in Ovaries by Five Months of Fetal Life
			Hormones of Female Cycle Control Folliculogenesis, Ovulation, and Condition of Uterus
			About Five to Twelve Primary Follicles Resume Development Each Month
			Single Follicle Becomes Dominant and Remainder Degenerate
			Why is Folliculogenesis Selectively Stimulated in Only a Few Follicles Each Month
			Resumption of Meiosis and Ovulation are Stimulated by Ovulatory Surge in FSH and LH
			Cumulus Oophorus Expands in Response to Ovulatory Surge
			Ovulation Depends on Breakdown of Follicle Wall
			Ruptured Follicle Forms Endocrine Corpus Luteum
		Menstrual Cycle
			Cleavage Subdivides Zygote Without Increasing its Size
			Segregation of Blastomeres into Embryoblast and Trophoblast Precursors
			Morula Develops Fluid-Filled Cavity and is Transformed into Blastocyst
		End of First Week: Initiating Implantation
			Blastocyst Hatches from Zona Pellucida Before Implanting
			Implantation in Abnormal Site Results in Ectopic Pregnancy
		Suggested Readings
Chapter 2
	2 - Second Week: Becoming Bilaminar and Fully Implanting
		Becoming Fully Implanted
		Embryoblast Reorganizes into Epiblast and Hypoblast
		Development of Amniotic Cavity
		Development of Yolk Sac and Chorionic Cavity
		Uteroplacental Circulatory System Begins to Develop During Second Week
		Suggested Readings
Chapter 3
	3 - Third Week: Becoming Trilaminar and Establishing Body Axes
		Overview of Gastrulation: Forming Three Primary Germ Layers and Body Axes
			Primitive Streak Forms at Beginning of Third Week and Marks Three Body Axes
			Formation of Definitive Endoderm
			Formation of Intraembryonic Mesoderm
			Formation of Ectoderm
		Specifics of Gastrulation: Moving Cells to New Locations and Making Organ Rudiments that Undergo Inductive Interactions
			Fate of Epiblast Cells Depends on Their Site of Origin
			Notochord is Formed in Multiple Steps
			Paraxial Mesoderm Differs in Head and Trunk
			Intermediate and Lateral Plate Mesoderm Forms Only in Trunk
		Formation of Neural Plate
		Primary Versus Secondary Body Development
		Suggested Readings
Chapter 4
	4 - Fourth Week: Forming the Embryo
		Tube-Within-A-Tube Body Plan Arises Through Body Folding
		Neurulation: Establishing Neural Tube, Rudiment of Central Nervous System
		Secondary Neurulation
		Cranial-Caudal Regionalization of Neural Tube
		Neural Crest Cells
			Neural Crest Cells Originate During Neurulation
			Neural Crest Cells Undergo Extensive Migration Along Well-Defined Pathways
			Neural Crest Cells Have Many Diverse Derivatives
				Cranial Neural Crest Cells
				Vagal Neural Crest Cells
				Trunk Neural Crest Cells
				Sacral/Lumbosacral Neural Crest Cells
		Somite Differentiation: Forming Dermamyotome and Sclerotome
		Suggested Readings
Chapter 5
	5 - Principles and Mechanisms of Morphogenesis and Dysmorphogenesis
		Principles of Morphogenesis and Dysmorphogenesis
		Animal Models
			Caenorhabditis elegans
			Xenopus laevis
		Using Animal Models to Predict Human Risk
		Experimental Techniques
			Classical Experimental Embryology
			Visualizing Gene Expression
			Manipulation of Gene Expression
				Manipulation of the Mouse Genome
		Signaling Pathways
			Patterning the DROSOPHILA Embryo: A Major Entry Point into Understanding Human Development
			Patterning the Vertebrate Embryo
				WNT Signaling
		Embryonic Stem Cells and Cloning
		Suggested Readings
Chapter 6
	6 - Fetal Development and the Fetus as a Patient
		During Fetal Period, Embryonic Organ Systems Mature and Fetus Grows
		Development of Placenta
		Development of Umbilical Cord
		Exchange of Substances Between Maternal and Fetal Blood in Placenta
			Erythroblastosis Fetalis
			Transfer of Cell-Free Fetal DNA to Maternal Plasma
			Placenta Allows Passage of Some Viral and Bacterial Pathogens
			HIV Can Be Transmitted Across Placenta During Parturition or in Breast Milk
			Teratogens Cross Placenta
		Intrauterine Growth Restriction
		Maternal Diabetes and Obesity
		Placenta Produces Several Important Hormones
		Production and Resorption of Amniotic Fluid
		Prenatal Diagnosis Assesses Health of Unborn
			Maternal Serum Screening
			Chorionic Villus Sampling
		Treating Fetus in Utero
		Fetal Cord Blood and Stem Cells
		Preterm Birth
		Suggested Readings
Chapter 7
	7 - Development of the Skin and Its Derivatives
			Other Types of Epidermal Cells
			Mesoderm Forms Dermis, Except in Face
		Development of Skin Derivatives
		Development of Hair
		Development of Sebaceous and Sweat Glands
		Development of Mammary Glands
		Development of Nails
		Suggested Readings
Chapter 8
	8 - Development of the Musculoskeletal System
		Tissue Origins and Differentiation of Musculoskeletal System
			Overview of Bone Development
			Overview of Muscle Development
		Somites Differentiate into Sclerotome and Dermamyotome
		Resegmentation of Sclerotomes
		Myotomes Develop at Segmental Levels
		Long Bone and Joint Development
		Development of Limb Muscles
		Suggested Readings
Chapter 9
	9 - Development of the Central Nervous System
		Structural Divisions of Nervous System
		Functional Divisions of Nervous System
		Primary Brain Vesicles Subdivide to Form Secondary Brain Vesicles
		Formation of Brain Flexures
		Cytodifferentiation of Neural Tube
		Differentiation of Spinal Cord
			Overview of Spinal Nerves
		Differentiation of Brain
			Brain Stem
				Overview of Cranial Nerves
				Organization of Columns
				Formation of Medulla Oblongata, Pons, and Cerebellum
			Higher Centers: Forebrain
				Pituitary Gland
		Growth of Brain
		Suggested Readings
Chapter 10
	10 - Development of the Peripheral Nervous System
		Structural Divisions of Nervous System
		Functional Divisions of Nervous System
		Origin of PNS
		Development of Trunk PNS
			Development of Spinal Nerves and Ganglia
				Ventral Column Motor Axons Are First to Sprout from Spinal Cord
				Somatic and Autonomic Motor Fibers Combine with Sensory Fibers to Form Spinal Nerves
				Axons in Spinal Nerves Grow to Specific Sites
			Pattern of Somatic Motor and Sensory Innervation is Segmental
			Pattern of Sympathetic Innervation is Not Entirely Segmental
				Sympathetic Innervation of Organs of Thorax and Head
				Sympathetic Innervation of Abdomen
				Parasympathetic Innervation of Lower Abdomen, Pelvis, and Perineum
		Development of Cranial PNS
			Development of Cranial Nerves and Sensory and Parasympathetic Ganglia
				Origin of Cranial Nerve Sensory Ganglia
				Origin of Cranial Nerve Parasympathetic Ganglia
		Suggested Readings
Chapter 11
	11 - Development of the Respiratory System and Body Cavities
		Development of Lungs and Respiratory Tree
		Partitioning of Coelom and Formation of Diaphragm
			Pericardial SAC is Formed by Pleuropericardial Folds that Grow from Lateral Body Wall in a Coronal Plane
			Pleuroperitoneal Membranes Growing from Posterior and Lateral Body Wall Seal Off Pericardioperitoneal Canals
			Diaphragm is a Composite Derived from Four Embryonic Structures
		Suggested Readings
Chapter 12
	12 - Development of the Heart
		Establishing Cardiac Lineage
		Formation of Primary Heart Tube
		Cardiac Looping
		Formation of Primitive Blood Vessels Associated with the Endocardial Tube
		Coordinated Remodeling of Heart Tube and Primitive Vasculature Produces Systemic and Pulmonary Circulations
		Septation of Heart
			Septation of Atria and Division of Atrioventricular Canal
			Realignment of Primitive Chambers
			Initiation of Septation of Ventricles
			Development of Atrioventricular Valves
			Septation of Outflow Tract and Completion of Ventricular Septation
			Development of Semilunar Valves
		Development of Pacemaker and Conduction System
		Development of Epicardium and Coronary Vasculature
		Suggested Readings
Chapter 13
	13 - Development of the Vasculature
		Formation of Blood and Vasculature Begins Early in Third Week
		Vasculogenesis and Angiogenesis
		Arteries Versus Veins
		Development of Aortic Arch Arteries
			Human Aortic Arch Arteries Arise in Craniocaudal Sequence and form Basket of Arteries Around Pharynx
			Aortic Arch Arteries give Rise to Important Vessels of Head, Neck, and Upper Thorax
		Dorsal Aorta Develops Ventral, Lateral, and Posterolateral Branches
			Vitelline Arteries give Rise to Arterial Supply of Gastrointestinal Tract
			Lateral Branches of Descending Aorta Vascularize Suprarenal Glands, Gonads, and Kidneys
			Intersegmental Branches Arise from Paraxial Mesoderm and Join Dorsal Aorta
			Umbilical Arteries Initially Join Dorsal Aortae but Shift Their Origin to Internal Iliac Arteries
			Arteries to Limbs are Formed by Remodeling of Intersegmental Artery Branches
		Primitive Embryonic Venous System is Divided into Vitelline, Umbilical, and Cardinal Systems
			Vitelline System Gives Rise to Liver Sinusoids, Portal System, and a Portion of Inferior Caval Vein
			Right Umbilical Vein Disappears and Left Umbilical Vein Anastomoses with Ductus Venosus
			Posterior Cardinal System is Augmented and then Superseded by Paired Subcardinal and Supracardinal Veins
			Blood is Drained from Head and Neck by Anterior Cardinal Veins
		Development of Lymphatic System
		Dramatic Changes Occur in Circulatory System at Birth
		Suggested Readings
Chapter 14
	14 - Development of the Gastrointestinal Tract
		Body Folding
		Dorsal Mesentery Initially Suspends Abdominal Gut Tube
		Three Regions of Primitive Gut
		Development of Abdominal Foregut
			Stomach Formation and Rotation
			Liver and Gallbladder Development
			Pancreas Development
		Spleen Development
		Ventral Mesentery Derivatives
		Midgut Development
			Primary Intestinal Loop
		Cytodifferentiation of Gut Endodermal Epithelium
		Development of Outer Intestinal Wall and its Innervation
		Hindgut Development
		Suggested Readings
Chapter 15
	15 - Development of the Urinary System
		Three Nephric Systems Arise During Development
			Formation of Pronephros and Mesonephric Duct
			Development of Mesonephros
			Development of Metanephros
		Relocation of Kidneys
		Contributions of Hindgut Endoderm to Urinary Tract
		Development of Suprarenal Gland
		Suggested Readings
Chapter 16
	16 - Development of the Reproductive System
		Reproductive System Arises with Urinary System
			Male Genital Development Begins with Differentiation of Sertoli Cells
			Development of Male Gametes
			Anti-Müllerian Hormone and Male Genital Development
				Differentiation of the Testis Leydig Cells
				Mesonephric Ducts and Accessory Glands of Male Urethra Differentiate in Response to Testosterone
		In Absence of Y Chromosome, Female Development Occurs
			Formation of Ovarian Primordial Follicles
			Paramesonephric Ducts Give Rise to Fallopian Tubes, Uterus, and Vagina, Whereas Mesonephric Ducts Degenerate
		Development of External Genitalia
			In Males, Urethral Groove Becomes Penile Urethra and Labioscrotal Swellings Form Scrotum
			In Females, Genital Tubercle Does Not Lengthen and Labioscrotal and Urethral Folds do not Fuse
		Suspension of Mesonephric-Gonadal Complex within Abdomen
		Development of Inguinal Canals
		Descent of Testes
		Ovaries become Suspended in Broad Ligament of Uterus and are Held High in Abdominal Cavity by Cranial Suspensory Ligaments
		Suggested Readings
Chapter 17
	17 - Development of the Pharyngeal Apparatus and Face
		Origin of Skull
		Development of Pharyngeal Arches
			Pharyngeal Apparatus
			Pharyngeal Arch Cartilages and Origin of Skeletal Elements
			Development of Temporomandibular Joint
			Origin of Vascular Supply
			Origin and Innervation of Musculature
				Additional Cranial Nerve Innervation
			Many Cranial Nerves are Mixed Nerves
		Development of Face
		Development of Nasal and Oral Cavities
		Development of Sinuses
		Fate of Pharyngeal Clefts
		Pharyngeal Arches Give Rise to Tongue
		Development of Thyroid Gland
		Development of Pharyngeal Pouches
		Development of Salivary Glands
		Development of Teeth
		Suggested Readings
Chapter 18
	18 - Development of the Ears
		Ear Consists of Three Individual Components
		Development of Inner Ear
		Development of Middle Ear
		Development of External Ear
		Suggested Readings
Chapter 19
	19 - Development of the Eyes
		Eye Originates from Several Embryonic Tissues Layers
		Development of Optic Cup and Lens
			Development of Neural Retina and Pigmented Epithelium
			Development of Optic Nerve
			Vascularization of Optic Cup and Lens
			Development of Choroid, Sclera, and Anterior Chamber
			Development of Cornea
			Development of Pupillary Membrane
			Development of Iris and Ciliary Body
		Development of Eyelids
			Suggested Readings
Chapter 20
	20 - Development of the Limbs
		Epithelial-Mesenchymal Interactions Control Limb Outgrowth
		Morphogenesis of Limb
		Tissue Origins of Limb Structures
		Differentiation of Limb Bones
		Innervation of Developing Limb
			Suggested Readings
Figure Credits
Document Text Contents
Page 1


Page 2

Larsen's Human
Gary C. SChoenwolf, PhD
University of Utah School of Medicine
Salt Lake City, Utah

Steven B. Bleyl, MD, PhD
University of Utah School of Medicine
Salt Lake City, Utah

PhiliP r. Brauer, PhD
Creighton University School of Medicine
Omaha, Nebraska

PhiliPPa h. franCiS-weSt, PhD
King's College London Dental Institute
London, United Kingdom


Page 263

Larsen's Human Embryology268

Clinical Taster

A full-term boy is born to a primigravid (first gestation)
mother after an uncomplicated pregnancy. The delivery goes
smoothly, with healthy Apgar scores of 8/10 at one minute
and 9/10 at five minutes. All growth parameters (length,
weight, and head circumference) are normal, ranging be-
tween the 10th and 25th centiles. The newborn examination
is also normal, and the infant is returned to his mother to
begin breast feeding.

Cranial lateral plate mesoderm initiates vasculogenesis to form
lateral endocardial tubes; myocardiogenesis begins

Lateral body folding brings endocardial tubes and surrounding
cardiogenic mesoderm together in thoracic region

Endocardial tubes surrounded by myocardium fuse to
form primary heart tube, which is divided into incipient
chambers by sulci

Atrioventricular sulcus

Myocardium invests endocardial heart tube and forms
cardiac jelly


Septum primum begins to form

Muscular ventricular
septum begins to form

Endocardial cushion tissues form

Outflow tract endocardial
cushions begin to form

Definitive atria and auricles are present

Foramen secundum and foramen ovale
form as septum primum meets
atrioventricular septum

Aortic and pulmonary outflow
tracts are fully separated by
fusion of outflow tract cushions;
ventricular septation is
completed by joining of
outflow tract, atrioventricular, and
muscular interventricular septa

endocardial cushions
fuse to form

Muscular ventricular
septum ceases to grow

Coronary sinus is formed

Semilunar and atrioventricular
valves are complete

Heart looping is complete

Heart begins to loop

Heart begins to beat

Weeks Days





















Time line. Formation of the heart.

The boy initially feeds well, but he becomes sleepy and
disinterested in feeding as the day progresses. At twenty hours
after birth, he exhibits decreased peripheral perfusion, cyanosis,
and lethargy. A pulse oximeter shows oxygen saturation in
the low 80% range (normal equals >90%) with increasing
respiratory distress. Paradoxically, blood oxygen saturation
worsens after administration of oxygen. The boy is emergently
transferred to the neonatal intensive care unit in worsening
shock. There, he is intubated, central intravascular catheters are
placed, and he is started on prostaglandins.

Page 264





First heart field





Second heart


Figure 12-1. Formation of the first heart field seen in ventral views. A, Location of cardiogenic progenitors in the early primitive streak. B, Location
of cardiogenic precursors (red gradated regions) within the mesoderm shortly after gastrulation and during initial specification. C, Location of the first
heart field (red) containing specified cardiogenic cells. The crescent-like arrangement of the progenitors is due to their migration pattern, local car-
diogenic induction signals, and development of the body folds. Medial and slightly caudal to the first heart field lies the second heart field (orange).


The heart is the first organ to function in human embryos.
It begins beating as early as the twenty-first day, and starts
pumping blood by the twenty-fourth to twenty-fifth day.
Much of cardiac development, including remodeling and
septation, occurs while the heart is pumping blood. This
is necessary to provide nutrients and oxygen and to dis-
pose of wastes during embryonic and fetal development,
but this mechanical and electrical activity also plays an
important role in the morphogenesis of the heart. The
embryonic heart is first morphologically identifiable as
a single tube composed of contractile myocardium sur-
rounding an inner endocardial (endothelial) tube, with
an intervening extracellular matrix. The heart is also
an asymmetrical organ whose left-right patterning is

established during gastrulation (left-right patterning is
covered in Chapter 3 and later in this chapter).

Cardiac progenitor cells are derived from intraem-
bryonic mesoderm emerging from the cranial third of the
primitive streak during early gastrulation. These progenitors
leave the primitive streak and migrate in a cranial-lateral
direction to become localized on either side of the primitive
streak (Fig. 12-1A, B). The cardiac progenitor cells eventually
become localized within the cranial lateral plate mesoderm
on both sides of the embryo, extending and arcing cranial
to the developing head fold, forming a cardiac crescent
(Fig. 12-1C). Cells in the cardiac crescent constitute the so-
called first heart field. It is thought that the cardiac cell
lineage is specified from mesodermal cells within the first
heart field. As discussed later, the first heart field is not the
sole source of cardiogenic cells for the developing heart, as
medial to the first heart field, there is already a population
of second heart field cells (Fig 12-1C).

In the Research Lab


To what degree cardiac progenitor cells within the epiblast and
the primitive streak are specified remains unknown. Activin and
Tgfβ produced by the hypoblast of the chick induce cardiogenic
properties in some of the overlying epiblast cells (Fig. 12-2A, B).
Other members of the Tgfβ superfamily, including nodal and
Vg1, also play a role in inducing cardiogenic properties in the
epiblast. During gastrulation, cardiac precursors residing in the
primitive streak are uncommitted, but these progenitors become
specified to become cardiogenic mesoderm soon after migrating
into the lateral plate. Mesp1 (mesoderm posterior 1) and Mesp2
(mesoderm posterior 2), members of the basic HLH family of
transcription factors, are expressed transiently during the primi-
tive streak stage. Both are required for migration of the cardiac
progenitor cells into the cranial region of the embryo, and both
have been implicated in the specification of the early cardiovascular

A chest x-ray shows cardiomegaly (enlarged heart) and
increased pulmonary vascularity (indicative of increased blood
flow). An echocardiogram shows a very small left ventricle
with a small aortic outflow tract, leading to the diagnosis of
hypoplastic left heart syndrome (HLHS).

HLHS is a shunt-dependent lesion: survival of these patients
depends on maintaining a patent ductus arteriosus (PDA)
to carry blood from the pulmonary artery to the aorta and out
to perfuse the systemic circulation. Supplemental oxygen lowers
resistance to pulmonary blood flow, causing blood to circulate
to the lungs instead of crossing the PDA. Thus, administering
supplemental oxygen actually decreases blood oxygen satura-
tion. Administration of prostaglandins prevents the physiological
closure of the ductus arteriosus, maintaining systemic perfusion
until surgery can be performed. The first-stage surgery, called
the Norwood procedure, connects the right ventricular outflow
tract to the aorta, and a separate shunt is used to provide blood
flow to the lungs. More surgeries follow at about six months and
two to three years of age. Occasionally, heart transplantation is
performed. The five-year survival rate for HLHS is around 70%.

Page 525

Figure Credits 531

Figure 17-4. A, Adapted from McBratney-Owen B,
Iseki S, Bamforth SD, et al. 2008. Development and
tissue origins of the mammalian cranial base. Dev Biol
322:121-132. B, C, Courtesy of Dr. Sachiko Iseki.

Figure 17-6. A, Courtesy of Dr. David Billmire.
C, Adapted from Morriss-Kay GM, Wilkie AO. 2005.
Growth of the normal skull vault and its alteration in
craniosynostosis: insights from human genetics and
experimental studies. J Anat 207:637-653.

Figure 17-7. A, Courtesy of Dr. Andrew Wilkie. Adapted
from Twigg SRF, Kan R, Babbs C, et al. 2004. Mutations
of ephrin-B1 (EFNB1), a marker of tissue boundary
formation, cause craniofrontonasal syndrome. Proc
Natl Acad Sci U S A 101:8652-8657. B, Courtesy of
Children's Hospital Medical Center, Cincinnati, Ohio.

Figure 17-8. B, Courtesy of Dr. Eiki Koyama. C, Courtesy
of Dr. Jun Doshisha. Adapted from Aoto K, Shikata Y,
Imai H, et al. 2009. Mouse Shh is required for prechordal
plate maintenance during brain and craniofacial
morphogenesis. Dev Biol 327:106-120.

Figure 17-9. A-C, Courtesy of Dr. Arnold Tamarin.
E, Courtesy of Dr. Robert E. Waterman.

Figure 17-14. A, Adapted from Lumsden A, Keynes R,
1989. Segmental patterns of neuronal development in
the chick hindbrain. Nature 337:424-428. B, Adapted
from Kontges G, Lumsden A. 1996. Rhombencephalic
neural crest segmentation is preserved throughout
craniofacial ontogeny. Development 122:3229-3242.

Figure 17-15. A, Courtesy of Dr. Abigail Tucker.
B, Courtesy of Dr. Moises Mallo. Adapted from Bobola
N, Carapuco M, Ohnemus S, et al. 2003. Mesenchymal
patterning by Hoxa2 requires blocking Fgf-dependent
activation of Ptx1. Development 130:3403-3414.

Figure 17-16. A, Courtesy of Drs. Susan Reijntjes and
Malcolm Maden. Adapted from Reijntjes S, Gale E,
Maden M. 2004. Generating gradients of retinoic
acid in the chick embryo: Cyp26C1 expression and a
comparative analysis of the Cyp26 enzymes. Dev Dyn
230:509-517. B, Adapted from Mark M, Ghyselinck
NB, Chambon P. 2004. Retinoic acid signalling in the
development of branchial arches. Curr Opin Genet Dev

Figure 17-17. A, B, Courtesy of Dr. Arnold Tamarin.
Figure 17-18. A, C, Courtesy of Dr. Arnold Tamarin.
Figure 17-19. A, B, Courtesy of Dr. Abigail Tucker.

Adapted from Tucker AS, Lumsden A. 2004. Neural crest
cells provide species-specific patterning information in
the developing branchial skeleton. Evol Dev 6:32-40.
C, Courtesy of Dr. Richard Schneider. Adapted from
Eames BF, Schneider RA. 2005. Quail-duck chimeras
reveal spatiotemporal plasticity in molecular and
histogenic programs of cranial feather development.
Development 132:1499-1509.

Figure 17-20. Courtesy of Dr. Michael Depew. Adapted
from Depew MJ, Lufkin T, Rubenstein JL. 2002.
Specification of jaw subdivisions by Dlx genes. Science

Figure 17-21. D, Courtesy of Dr. Arnold Tamarin.
Figure 17-22. B, Courtesy of Dr. Arnold Tamarin.
Figure 17-23. Courtesy of Children's Hospital Medical

Center, Cincinnati, Ohio.
Figure 17-28. C, Courtesy of Dr. Arnold Tamarin.

Figure 17-29. With permission from Dr. Robin Krimm.
Adapted from Ma L, Lopez GF, Krimm RF. 2009.
Epithelial-derived BDNF is required for gustatory
neuron targeting during a critical developmental period.
J Neurosci 29:3354-3364.

Figure 17-34. Adapted from Irving D, Willhite C,
Burk D. 1986. Morphogenesis of isotretinoin-induced
microcephaly and micrognathia studied by scanning
electron microscopy. Teratology 34:141-153.

Figure 17-35. E, Courtesy of Dr. Abigail Tucker.
Figure 17-36. Courtesy of Drs. YiPing Chen and Yanding

Zhang. Adapted from Zhang YD, Chen Z, Song YQ, et al.
2005. Making a tooth: growth factors, transcription
factors, and stem cells. Cell Res 15:301-316.

Figure 17-37. Courtesy of Dr. Abigail Tucker.
Figure 17-38. A-G, Courtesy of Dr. Martyn Cobourne.

C, G, Adapted from Cobourne MT, Sharpe PT. 2013.
Disease of the tooth: the genetic and molecular basis of
inherited anomalies affecting the dentition. WIREs Dev
Biol 2:183-212.

Figure 17-39. A, B, Courtesy of Dr. Jodi L. Smith.
Figure 18-1. A, Courtesy of the family. B, Courtesy of

Drs. Nancy Bonini and Derek Lessing.
Figure 18-2. A, Courtesy of Dr. Robert E. Waterman.

B, G, Adapted from Kikuchi T, Tonosaki A, Takasaka T.
1988. Development of apical-surface structures of
mouse otic placode. Acta Otolaryngol 106:200-207.

Figure 18-4. Courtesy of Dr. Doris K. Wu. Adapted from
Morsli H, Choo D, Ryan A, et al. 1998. Development of
the mouse inner ear and origin of its sensory organs.
J Neurosci 18:3327-3335.

Figure 18-5. A, Courtesy of Dr. Suzanne L. Mansour and
C. Albert Noyes. B, Adapted from Kelley MW. 2006.
Regulation of cell fate in the sensory epithelia of the
inner ear. Nat Rev Neurosci 7:837-849.

Figure 18-6. Adapted from Riccomagno MM, Takada S,
Epstein DJ. 2005. Wnt-dependent regulation of inner
ear morphogenesis is balanced by the opposing and
supporting roles of Shh. Genes Dev 19:1612-1623.

Figure 18-8. A, B, Adapted from Barald KF, Kelley MW.
2004. From placode to polarization: new tunes in inner ear
development. Development 131:4119-4130. C, Adapted
from Frolenkov GI, Belyantseva IA, Friedman TB, Griffith
AJ. 2004. Genetic insights into the morphogenesis of inner
ear hair cells. Nat Rev Genet 5:489-498. D, Adapted from
Kelley MW. 2006. Regulation of cell fate in the sensory
epithelia of the inner ear. Nat Rev Neurosci 7:837-849.

Figure 18-10. Adapted from Kelley MW. 2006.
Regulation of cell fate in the sensory epithelia of the
inner ear. Nat Rev Neurosci 7:837-849.

Figure 18-11. A, Courtesy of Dr. Gregory Frolenkov.
Adapted from Frolenkov GI, Belyantseva IA, Friedman TB,
Griffith AJ. 2004. Genetic insights into the morphogenesis
of inner ear hair cells. Nat Rev Genet 5:489-498. B, C,
Courtesy of Dr. Jenny Murdoch. Adapted from Curtin JA,
Quint E, Tsipouri V, et al. 2003. Mutation of Celsr1 disrupts
planar polarity of inner ear hair cells and causes severe
neural tube defects in the mouse. Curr Biol 13:1129-1133.

Figure 18-12. Adapted from Dahlen RT, Harnsberger HR,
Gray SD, et al. 1997. Overlapping thin-section fast spin-
echo MR of the large vestibular aqueduct syndrome.
AJNR Am J Neuroradiol 18:67-75.

Page 526

Figure Credits532

Figure 18-13. Adapted from Steel KP, Kros CJ. 2001. A
genetic approach to understanding auditory function.
Nat Genet 27:143-149.

Figure 18-14. A, Courtesy of Dr. Arnold Tamarin.
Figure 18-15. A, B, C, D, F, Courtesy of Dr. Roger E.

Stevenson. Adapted from Carey JC. 2006. Ear. In
Stevenson RE, Hall JG (eds): Human Malformations and
Related Anomalies. Second Edition. Oxford University
Press, London, pp. 327-371. E, Courtesy of Dr. John C.
Carey and Meg Weist. Adapted from Kumar S, Marres HA,
Cremers CW, Kimberling WJ. 1998. Autosomal-dominant
branchio-otic (BO) syndrome is not allelic to the branchio-
oto-renal (BOR) gene at 8q13. Am J Med Genet 76:395-401.

Figure 19-1. A, Courtesy of Dr. Robert E. Waterman.
C, Adapted from Morriss-Kay GM. 1981. Growth and
development of pattern in the cranial neural epithelium
of rat embryos during neurulation. J Embryol Exp
Morphol 65 Suppl:225-241. E, Adapted from Garcia-
Porrero JA, Colvee E, Ojeda JL. 1987. Retinal cell death
occurs in the absence of retinal disc invagination:
experimental evidence in papaverine-treated chicken
embryos. Anat Rec 217:395-401. I, Adapted from Morse
DE, McCann PS. 1984. Neuroectoderm of the early
embryonic rat eye. Scanning electron microscopy.
Invest Ophthalmol Vis Sci 25:899-907.

Figure 19-3. A, B, Courtesy of Dr. Arnold Tamarin.
Figure 19-6. A, B, Courtesy of Dr. Sabine Fuhrmann.

C, Adapted from Martinez-Morales JR, Rodrigo I, Bovolenta
P. 2004. Eye development: a view from the retina
pigmented epithelium. Bioessays 26:766-777. D, Adapted
from Ashery-Padan R, Gruss P. 2001. Pax6 lights-up the
way for eye development. Curr Opin Cell Biol 13:706-714.

Figure 19-7. B, Courtesy of Dr. Arnold Tamarin.
Figure 19-8. Adapted from Traboulsi EI. 2006. Eye. In

Stevenson RE, Hall JG (eds): Human Malformations and
Related Anomalies. Second Edition. Oxford University
Press, London, pp. 297-325.

Figure 20-1. Courtesy of Freddie Astbury. Adapted from
Thalidomide UK (

Figure 20-2. A, Courtesy of Dr. Robert E. Waterman. B-D,
Adapted from Kelley RO. 1985. Early development of
the vertebrate limb: an introduction to morphogenetic
tissue interactions using scanning electron microscopy.
Scan Electron Microsc (Pt 2):827-836.

Figure 20-3. A, C, Adapted from Alberts B, Johnson,
A, Lewis J, et al. 2002. Molecular Biology of the Cell.
Fourth Edition. Garland Science, New York.

Figure 20-4. Adapted from Mariani FV, Martin GR.
2003. Deciphering skeletal patterning: clues from the
limb. Nature 423:319-325.

Figure 20-5. Courtesy of Drs. Sheila Bell and W. Scott.
Figure 20-6. B, Courtesy of Dr. Martin J. Cohn. Adapted

from Cohn MJ, Izpisua-Belmonte JC, Abud H, et al.
995. Fibroblast growth factors induce additional limb
development from the flank of chick embryos. Cell

Figure 20-7. Adapted from Mariani FV, Martin GR.
2003. Deciphering skeletal patterning: clues from the
limb. Nature 423:319-325.

Figure 20-8. Adapted from Izpisua-Belmonte JC, Duboule
D. 1992. Homeobox genes and pattern formation in
the vertebrate limb. Dev Biol 152:26-36.

Figure 20-9. Adapted from Davis AP, Witte DP,
Hsieh-Li HM, et al. 1995. Absence of radius and
ulna in mice lacking hoxa-11 and hoxd-11. Nature

Figure 20-10. Courtesy of Dr. Mario Capecchi. Adapted
from Wellik DM, Capecchi MR. 2003. Hox10 and Hox11
genes are required to globally pattern the mammalian
skeleton. Science 301:363-367.

Figure 20-12. A, Courtesy of Dr. Arnold Tamarin. B, C,
Courtesy of Dr. Robert E. Waterman.

Figure 20-13. Adapted from Alberts B, Johnson A, Lewis
J, et al. 2002. Molecular Biology of the Cell. Fourth
Edition. Garland Science, New York.

Figure 20-14. A, Courtesy of Dr. Rolf Zeller. Adapted
from Panman L, Zeller R. 2003. Patterning the limb
before and after SHH signalling. J Anat 202:3-12.
C, D, Courtesy of Dr. Cliff Tabin. Adapted from Harfe
BD, Scherz PJ, Nissim S, et al. 2004. Evidence for an
expansion-based temporal Shh gradient in specifying
vertebrate digit identities. Cell 118:517-528.

Figure 20-15. Courtesy of Dr. Rolf Zeller. Adapted from te
Welscher P, Zuniga A, Kuijper S, et al. 2002. Progression
of vertebrate limb development through SHH-mediated
counteraction of GLI3. Science 298:827-830.

Figure 20-16. Adapted from Chan DC, Laufer E, Tabin
C, Leder P. 1995. Polydactylous limbs in Strong's
Luxoid mice result from ectopic polarizing activity.
Development 121:1971-1978.

Figure 20-18. B, Courtesy of Dr. Sigmar Stricker. Adapted
from Stricker S, Mundlos S. 2011. Mechanisms of digit
formation: human malformation syndromes tell the
story. Dev Dyn 240:990-1004.

Figure 20-19. A, B, C, E, Courtesy of Children's Hospital
Medical Center, Cincinnati, Ohio. D, Courtesy of Dr.
David Vischokil. F, Courtesy of Dr. John C. Carey.

Figures 20-20, 20-21. Courtesy of Dr. Irene Hung.
Figure 20-22. A, Courtesy of Children's Hospital

Medical Center, Cincinnati, Ohio. B, C, Courtesy of
Dr. Thomas Lufkin. Adapted from Kraus P, Lufkin T.
2006. Dlx homeobox gene control of mammalian
limb and craniofacial development. Am J Med Genet A

Figure 20-23. Courtesy of Muragaki Y, Mundlos S,
Upton J, Olsen BR. 1996. Altered growth and branching
patterns in synpolydactyly caused by mutations in
HOXD13. Science 272:548-551.

Figures 20-24, 20-25. Courtesy of Dr. Irene Hung.
Figure 20-26. Adapted from Tosney KW, Landmesser

LT. 1985. Development of the major pathways for
neurite outgroth in the chick hindlimb. Dev Biol

Figure 20-27. Adapted from Tosney KW, Landmesser
LT. 1984. Pattern and specificity of axonal outgrowth
following varying degrees of chick limb bud ablation.
J Neurosci 4:2518-2527.

Figure 20-29. A, B, D, Adapted from Kania A, Johnson RL,
Jessell TM. 2000. Coordinate roles for LIM homeobox
genes in directing the dorsoventral trajectory of
motor axons in the vertebrate limb. Cell 102:161-173.
C, Adapted from Shirasaki R, Pfaff SL. 2002. Transcriptional
codes and the control of neuronal identity. Annu Rev
Neurosci 25:251-281.

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