Table of Contents
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Introduction |
1 |
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Why Study Human Embryology? |
2 |
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Link Between Development and
Cancer |
3 |
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Periods of Human Embryology |
4 |
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Note About Gene Names |
4 |
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Why do We Age |
5 |
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Progeria: Premature Aging |
6 |
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Phases of Human Embryology |
6 |
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Period of Egg and Embryo:
Summary of Main Events |
8 |
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Body Axes: Understanding
Embryonic Coordinates |
9 |
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Want to Learn More? |
12 |
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1 |
Gametogenesis, Fertilization, and First Week |
15 |
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Primordial Germ Cells |
17 |
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Teraioma Formation |
18 |
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Origin of Pgcs |
19 |
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Molecular Regulation of PGC
Development |
19 |
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Gametogenesis |
20 |
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Why is Timing of Gametogenesis
Different in Males and Females? |
20 |
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Spermatogenesis |
25 |
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Spermatozoa Abnormalities |
25 |
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Oogenesis |
28 |
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Chromosomal Abnormalities Result
in Spontaneous Abortion or Abnormal Development |
32 |
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Many Chromosomal Anomalies Arise
During Gametogenesis
and Cleavage |
32 |
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Chromosome Analysis can
Determine Parental Source of Defective Chromosome and Provides Basis for
Diagnosis and Possible Treatment |
34 |
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Ovulation |
35 |
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Menstrual Cycle |
37 |
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Fertilization |
39 |
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Cleavage |
41 |
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What Determines Whether a Blastomere
will form Inner Cell Mass R Trophoblast? |
43 |
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End of First Week: Initiating
Implantation |
43 |
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Contraception |
44 |
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Assisted Reproductive Technology |
46 |
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2 |
Second Week: Becoming Bilaminar
and Fully Implanting |
51 |
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Becoming Fully Implanted |
53 |
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What Regulates the Initial Phase
of Implantation: Blastocyst Adherence to the
Uterine Epithelium? |
53 |
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Why isn’t Conceptus Rejected by its
Mother? |
55 |
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Initiating Endoderm Formation |
56 |
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Development of Amniotic Cavity |
57 |
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Development of Yolk Sac and Chorionic
Cavity |
57 |
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Uteroplacental Circulatory System Begins to
Develop During Second Week |
58 |
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Hydatidiform Moles |
60 |
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Genomic Imprinting |
64 |
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X Inactivation |
67 |
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X Inactivation Affects
Inheritance of Congenital Disease |
67 |
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Genomic Imprinting Affects
Inheritance of Congenital Disease |
67 |
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3 |
Third Week: Becoming Trilaminar
and Establishing Body Axes |
69 |
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Overview of Gastrulation:
Forming Three Primary Germ Layers and Body Axes |
71 |
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Induction of Primitive Streak |
71 |
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Cellular Basis of Primitive
Streak Formation |
72 |
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Establishing Left-Right Axis |
73 |
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Development in Animal Models
versus Humans |
76 |
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Cellular Basis of Gastrulation |
80 |
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Establishing Medial-Lateral
Subdivisions of Mesoderm |
81 |
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Specifics of Gastrulation:
Moving Cells to New Locations and Making Organ Rudiments that Undergo
Inductive Interactions |
83 |
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Cellular Basis of Convergent
Extension |
87 |
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Molecular Mechanism of Somitogenesis |
88 |
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Abnormal Gastrulation
Leads to Caudal Dysplasia |
92 |
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Formation of Neural Plate |
94 |
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Neural Induction |
94 |
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Head, Trunk, and Tail Organizers |
97 |
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Primary versus Secondary Body
Development |
97 |
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4 |
Fourth Week: Forming the Embryo |
101 |
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Tube-within-a-Tube Body Plan
Arises through Body Folding |
103 |
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Anterior Body Wall Defects |
106 |
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Neurulation: Establishing the Neural Tube,
the Rudiment of the Central Nervous System |
107 |
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Mechanisms of Tieurulation |
110 |
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Actin-Binding Protiens
and Apical Constriction |
112 |
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Dorsal-Ventral Patterning of the Neural Tube |
112 |
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Neural Tube Defects (NTDs) |
113 |
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Secondary Neurulation |
117 |
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Cranial-Caudal Regionalization
of the Neural Tube |
117 |
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Neural Crest Cells |
119 |
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Epithelial-to-Mesenchymal
Transformation (EMT) |
119 |
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What Local Factors Guide
Migration of Neural Crest Cells? |
121 |
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Mutants Provide Information
About Mechanisms of Neural Crest Cell Migration and Developmental Restriction |
122 |
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Survival and Differentiation of
Peripheral Neurons |
128 |
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Neural Crest Cell Disease: Neurocristopathies |
128 |
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Somite Differentiation: Forming
Dermatome, Myotome, and Sclerotome |
128 |
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Inductive Interactions Underlie
Formation of Somite Subdivisions |
128 |
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Spinal Anomalies |
130 |
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5 |
Principles and Mechanisms of Morphogenesis and Dysmorphogenesis |
133 |
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Principles of Morphogenesis and Dysmorphogenesis |
133 |
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Animal Models |
135 |
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Experimental Techniques |
142 |
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Signaling Pathways |
150 |
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Embryonic Stem Cells and Cloning |
162 |
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6 |
Fetal Development and the Fetus as Patient |
167 |
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During Fetal Period, Embryonic
Organ Systems Mature and Fetus Grows |
169 |
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Development of Placenta |
170 |
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Development of Umbilical Cord |
171 |
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Exchange of Substances Between
Maternal and Fetal Blood in Placenta |
173 |
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Intrauterine Growth Restriction |
178 |
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Maternal Diabetes and Obesity |
178 |
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Placenta Produces Several
Important Hormones |
179 |
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Production and Resorption
of Amniotic Fluid |
179 |
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Twinning |
179 |
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Prenatal Diagnosis Assesises
Health of Unborn |
180 |
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Treating Fetus in Utero |
186 |
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Fetal Cord Blood and Stem Cells |
189 |
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7 |
Development of the Skin and its Derivatives |
193 |
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Origin of Epidermis and Dermis
of Skin |
195 |
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Molecular Regulation of Skin
Differentiation |
197 |
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Inherited Skin Diseases |
198 |
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Development of Skin Derivatives |
202 |
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Anomalies of Skin Derivatives |
202 |
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Regulation of Hair Patterning
and Differentiation |
205 |
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Hair Anomalies |
206 |
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Wnt Signaling and Development of
Mammary Gland |
209 |
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Tooth Induction |
214 |
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Tooth Anomalies |
214 |
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8 |
Development of the Musculoskeletal System |
217 |
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Tissue Origins and
Differentiation of Musculoskeletal System |
219 |
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Commitment to Musculoskeletal
Lineage |
221 |
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Somites Differentiate into Sclerotome,
Myotome,
and Dermatome |
222 |
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Resegmentation of Sclerotomes |
217 |
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Subdivision of Sclerotome |
222 |
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Specification of Vertebrae
Identity |
227 |
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Vertebral Defects |
230 |
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Myotomes and Dermatomes Develop at
Segmental Levels |
231 |
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Myogenic Commitment in Somite |
234 |
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Long Bone and Joint Development |
234 |
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Molecular Regulation of Bone and
Joint Development |
237 |
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Defects in Skeletal Development |
239 |
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Development of Limb Muscles |
241 |
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Migration of Muscle Progenitors |
242 |
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Muscle Cell and Fiber Type
Commitment |
244 |
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Regional Differences in
Development of Muscles |
244 |
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Muscular Dystrophy |
244 |
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9 |
Development of the Central Nervous System |
247 |
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Structural Divisions of Nervous
System |
251 |
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Functional Divisions of Nervous
System |
251 |
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Primary Brain Vesicles Subdivide
to form Secondary Brain Vesicles |
251 |
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Positional Information Patterns
Neural Plate and Tube |
253 |
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Formation of Brain Flexures |
255 |
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Cytodifferentiation of Neural Tube |
255 |
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Differentiation of Spinal Cord |
257 |
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Differentiation of Brain |
258 |
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Cellular and Molecular Basis of Cerebellar
Malformations and Dysfunction |
267 |
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Mouse Mutants with Cerebellar
Ataxias |
269 |
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Development of Visual System:
Example of How Nervous System Wires itself |
274 |
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Congenital Malformations of
Cerebral Cortex |
285 |
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Kallmann Syndrome |
287 |
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Growth of the Brain |
290 |
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Brain Size |
290 |
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10 |
Development of the Peripheral Nervous System |
297 |
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Structural Divisions of Nervous
System |
299 |
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Functional Divisions of Nervous
System |
299 |
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Origin of PNS |
300 |
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Specification and Plasticity of
Precursor Cells of PNS |
300 |
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Neural Crest Cells and their
Derivatives as Stem Cells |
301 |
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Neurofibromatosis Type 1 (NF-1) |
302 |
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Neurogenesis in PNS |
302 |
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Development of Trunk PNS |
303 |
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Hereditary Peripheral
Neuropathies |
306 |
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Regulating Axonal Guidance in PNS |
311 |
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Development of Cranial PNS |
313 |
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11 |
Development of the Respiratory System and Body
Cavities |
319 |
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Development of Lungs and
Respiratory Tree |
321 |
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Developmental Abnormalities of
Lung and Respiratory Tree |
324 |
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Lung Maturation and Survival of
Premature Infants |
325 |
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Approaches for Studying Lung
Development and Branching Morphogenesis |
327 |
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Drosophila Tracheal System
Development |
328 |
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Partitioning of Coelom
and Formation of Diaphragm |
329 |
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Diaphragmatic Defects and
Pulmonary Hypoplasia |
334 |
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Oligohydramnios and Pulmonary Hypoplasia |
334 |
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Congenital Diaphragmatic Hernia |
335 |
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12 |
Development of the Heart |
337 |
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Formation of Primitive Heart
Tube Specification of Cardiac Progenitor |
340 |
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Role of Secondary Heart Field in
Formation of Outflow Segment of Heart |
349 |
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Gene Mutations Target Primary
and Secondary Heart Fields |
349 |
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Cardiac Looping |
350 |
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Formation of Primitive Blood
Vessels Associated with Endocardial Tube |
350 |
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Mechanisms Driving Cardiac
Bending and Looping |
352 |
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Sidedness in Heart Looping |
353 |
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Subregions of Heart are Specified Early in
Development |
354 |
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Coordinated Remodeling of Heart
Tube and Primitive Vasculature Produces Systemic and Pulmonary Circulations |
355 |
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Septation of Heart |
360 |
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Epithelial-to-Mesenchymal
Transformation During Endocardial Cushion Cell
Formation |
361 |
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Effects of Hyperglycemia and
Hypoxia on Cushion Tissue Formation |
362 |
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Myocardium Develops Two Layers |
369 |
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Neural Crest Cell Contribution to Outflow Tract Septation |
375 |
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Many Heart Defects may be
Related to Interactions Between Secondary Heart Field and Neural Crest Cells |
376 |
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Development of Pacemaker and
Conduction System |
376 |
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Development of Epicardium
and Coronary Vasculature |
377 |
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Frequency and Etiology of
Cardiovascular Malformations |
378 |
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Common Heart Malformations |
378 |
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Known Genetic Causes of Heart
Malformations |
382 |
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22q11.2 Deletions and Heart
Malformations |
383 |
|
13 |
Development of the Vasculature |
385 |
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Formation of Vasculature Begins
Early in Third Week |
388 |
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Second Source of Hematopoieuc
Stem Cells |
390 |
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Intraembryonic Hematopoietic
Stem Cells may be Source OT Definitive Hematopoietic Stem Cells |
390 |
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Vasculogenesis |
392 |
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Methods for Visualizing Blood
Vessel Formation |
392 |
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What Initiates and Controls Vasculogenesis? |
393 |
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Angiogenesis Expands and
Remodels Initial Vascular Complex |
395 |
|
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Formation of Arteries versus
Veins |
397 |
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Angiomas |
399 |
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Hereditary Hemorrhagic Telangiectasia |
401 |
|
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Treatment of
Corticosteroid-Resistant Hemangiomas in Humans |
401 |
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Development of Aortic Arches |
402 |
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Tissue Interactions Direct
Pharyngeal Aortic Arch Remodeling |
407 |
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Dorsal Aorta Develops Ventral,
Lateral, and Posterolateral Branches |
408 |
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Vascular Anomalies Arising from
Errors in Remodeling of Great Vessels |
413 |
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Formation of “Vascular Rings”
that Constrict Esophagus and Trachea |
413 |
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Coarctation of the Aorta |
415 |
|
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Primitive Embryonic Venous
System is Divided into Vitelline, Umbilical, and
Cardinal Systems |
419 |
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Vena Cava Anomalies |
424 |
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Development of Lymphatic System |
425 |
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Molecular Mechanisms of
Lymphatic Development |
428 |
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Lymphedema may Result from Lymphatic Hypoplasia |
428 |
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Dramatic Changes Occur in
Circulatory System At Birth |
429 |
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Patent Ductus Arteriosus
Leads to Heart Failure if Not Corrected |
432 |
|
14 |
Development of the Gastrointestinal Tract |
435 |
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Body Folding |
437 |
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Dorsal Mesentery Initially
Suspends Abdominal Gut Tube |
439 |
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Three Regions of Primitive Gut |
441 |
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Regionalization of Gut Tube
Demarcates Sites of Organ Formation |
442 |
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Development of Abdominal Foregut |
445 |
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Hepatoblast Specification and Fate |
449 |
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Abnormal Formation and Rotation
of Ventral Pancreas |
452 |
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Notch Signaling and Pancreatic
Cell Lineage Determination |
452 |
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Regulation of Number of Islet
Cells |
454 |
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Development |
454 |
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Derivatives of Ventral Mesentery |
454 |
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Development of Midgut |
456 |
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Abnormal Rotation and Fixation
of Midgut |
456 |
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Defects of the Umbilicus and
Anterior Abdominal Wall |
458 |
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Cytodifferentiation of Endodermal
Epithelium of Gut |
462 |
|
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Differentiation of
Gastrointestinal Tract Epithelium |
464 |
|
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Faulty Wnt
Signaling and Β-Catenin Turnover is Often a
Prelude to Colon Cancer |
465 |
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Development of Outer Intestinal
Wall and its Innervation |
467 |
|
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Hirschsprung Disease |
470 |
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Irritable Bowel Syndrome |
470 |
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Infantile Hypertrophic
Pyloric Stenosis |
470 |
|
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Hirschsprung Disease and Neural Crest Cell
Defects |
471 |
|
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Development of Hindgut |
472 |
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Hindgut Abnormalities and
Associated Abdominal Wall Defects |
475 |
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Urachal Anomalies |
475 |
|
15 |
Development of the Urogenital
System |
479 |
|
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Three Nephric
Systems Develop |
483 |
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Formation of Nephric
Lineage |
486 |
|
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Factors Expressed in Metanephric
Mesoderrn
Regulate Induction of Budding Branching of the Ureteric
Bud |
490 |
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Signals from Ureteric
Bud Induce Nephrogenic Mesoderm to Condense While Mesoderm
Drives Continual Ureteric Branching and Growth |
490 |
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Influences Between Ureteric
Bud and Metanephric
Blastema
Induce Formation of Nephron through Mesenchymal-to-Epithelial
Conversion of Blastema |
493 |
|
|
Renal Agenesis and Dysplasia |
493 |
|
|
Mutations Causing Nephron
Pathologies |
494 |
|
|
Congenital Polycystic Kindney
Disease |
495 |
|
|
Ascent of Kidneys |
495 |
|
|
Contributions of Hindgut
Endoderm to Urinary Tract |
495 |
|
|
Urinary Tract Anomalies |
497 |
|
|
Development of Suprarenal Gland |
499 |
|
|
Congenital Adrenal Hyperplasia |
500 |
|
|
Genital System Arises with
Urinary System |
500 |
|
|
Initiating Male versus Female
Development |
503 |
|
|
Sox9 Gene is Likely a Primary
Target of Sry Expression |
505 |
|
|
Sertoli Cells are Main Organizer of
Testes |
505 |
|
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Sex Reversal |
508 |
|
|
Hermaphrodites |
508 |
|
|
Müllerian Duct Regression and Amh-Mediated
Upregulation
of Metalloproteinase Expression |
509 |
|
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Mutations in Amh or
its Receptor Causes Persistent Müllerian Duct Syndrome in
XY Individuals |
509 |
|
|
Differentiation of Leydig
Cells |
510 |
|
|
Development of the Epididymus,
Vas Deferens, and Seminal Vesicles |
512 |
|
|
Cystic Fibrosis Transmembrane
Conductance Regulator is Required for Vas Deferens Development |
512 |
|
|
Development of Prostate Gland |
512 |
|
|
In Absence of Y Chromosome,
Female Development Occurs |
515 |
|
|
Female Gonadogenesis
is not a Simple Matter of Default |
516 |
|
|
Müllerian Duct Development and
Regionalized Expression of Hox Genes |
518 |
|
|
Anomalies of Uterus |
520 |
|
|
Diethylstilbestrol Causes
Several Reproductive Anomalies |
520 |
|
|
Development of External Genitalia |
521 |
|
|
Formation of External Genitalia |
522 |
|
|
Suspension of Mesonephric-Gonadal
Complex within Adbomen |
525 |
|
|
Development of the Inguinal
Canals |
525 |
|
|
Descent of the Testes |
526 |
|
|
Cryptorchidism |
530 |
|
|
Ovaries Become Suspended in
Broad Ligament of Uterus and are Held High in Abdominal Cavity by Cranial Suspensory
Ligaments |
530 |
|
|
Pseudohermaphrodism |
531 |
|
|
Defective Partitioning of Cloaca |
536 |
|
16 |
Development of the Pharyngeal Apparatus and Face |
543 |
|
|
Origin of Skull |
545 |
|
|
Holoprosencephaly |
547 |
|
|
Craniosynostosis |
550 |
|
|
Development of Pharyngeal Arches |
551 |
|
|
Hindbrain is Segmented |
560 |
|
|
Retinoic Acid Acts in Normal and
Abnormal Development of Head and Neck |
560 |
|
|
Development of Face |
563 |
|
|
Outgrowth of Facial Prominences
is Regulated by Epithelial-Mesenchymal Interactions |
564 |
|
|
Patterning of Facial Prominences
is Regulated by Epithelial-Mesenchymal Interactions |
566 |
|
|
Dlx Code Patterns the First
Pharyngeal Arch |
566 |
|
|
Development of Nasal and Oral
Cavities |
568 |
|
|
Facial Clefting |
569 |
|
|
Development of Sinuses |
571 |
|
|
Fate of Pharyngeal Clefts |
572 |
|
|
Pharyngeal Arches Give Rise to
Tongue |
573 |
|
|
Development of Thyroid Gland |
576 |
|
|
Development of Pharyngeal Pouches |
576 |
|
|
Development of Salivary Glands |
578 |
|
|
Causes of Craniofacial Anomalies |
579 |
|
|
Cranialfacial Syndromes |
580 |
|
17 |
Development of the Ears and Eyes |
583 |
|
|
Ear Development |
588 |
|
|
Induction and Patterning of
Rudiments of Inner Ear |
588 |
|
|
Formation of Sensory Cells |
593 |
|
|
Malformations of Inner Ear: Sensorineural
Hearing Loss |
597 |
|
|
Malformations of External and
Middle Ear: Conductive Hearing Loss |
601 |
|
|
Eye Development |
602 |
|
|
Formation of Eye Field |
602 |
|
|
Formation and Morphogenesis of
Lens |
604 |
|
|
Patterning of Eye |
608 |
|
|
Differentiation of Pigmented
Epithelium |
610 |
|
|
Regulation of Proliferation and
Differentiation of Retinal Progenitor Cells |
610 |
|
|
Abnormalities of Eye |
613 |
|
18 |
Development of the Limbs |
617 |
|
|
Epithelial-Mesenchymal
Interactions Control Limb Outgrowth |
619 |
|
|
Patterning of Limb Bud |
621 |
|
|
Growth and Patterning Along
Proximal-Distal Axis |
621 |
|
|
Morphogenesis of Limb Bud |
626 |
|
|
Specification of Cranial-Caudal
Axis |
628 |
|
|
Specification of Dorsal-Ventral
Axis |
630 |
|
|
Cessation of Limb Outgrowth and
Morphogenesis of Autopod |
630 |
|
|
Congenital Anomalies of Limbs |
632 |
|
|
Tissue Origins of Limb Structures |
639 |
|
|
Differentiation of Limb Bones |
639 |
|
|
Innervation of Developing Limb Bud |
640 |
|
|
Specification and Projection of
Limb Motor Axons |
642 |
|
|
Figure Credits |
645 |
|
|
Index |
653 |
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