Anatomy, Histology,
and Cell Biology
PreTest
TM
Self-Assessment and Review
Notice
Medicine is an ever-changing science. As new research and clinical experience
broaden our knowledge, changes in treatment and drug therapy are required. The
editors and the publisher of this work have checked with sources believed to be reli-
able in their efforts to provide information that is complete and generally in accord
with the standards accepted at the time of publication. However, in view of the pos-
sibility of human error or changes in medical sciences, neither the editors nor the
publisher nor any other party who has been involved in the preparation or publi-
cation of this work warrants that the information contained herein is in every
respect accurate or complete, and they are not responsible for any errors or omis-
sions or for the results obtained from use of such information. Readers are encour-
aged to confirm the information contained herein with other sources. For example
and in particular, readers are advised to check the product information sheet
included in the package of each drug they plan to administer to be certain that the
information contained in this book is accurate and that changes have not been
made in the recommended dose or in the contraindications for administration. This
recommendation is of particular importance in connection with new or infre-
quently used drugs.
Anatomy, Histology, and
Cell Biology
PreTest
TM
Self-Assessment and Review
Third Edition
Robert M. Klein, PhD

Professor and Associate Dean
Professional Development and Faculty Affairs
Department of Anatomy and Cell Biology
University of Kansas, School of Medicine
Kansas City, Kansas
George C. Enders, PhD
Associate Professor and Director
of Medical Education
Department of Anatomy and Cell Biology
University of Kansas, School of Medicine
Kansas City, Kansas
New York Chicago San Francisco Lisbon London Madrid Mexico City
Milan New Delhi San Juan Seoul Singapore Sydney Toronto
Copyright © 2007 by The McGraw-Hill Companies, Inc. All rights reserved. Manufactured in the
United States of America. Except as permitted under the United States Copyright Act of 1976, no
part of this publication may be reproduced or distributed in any form or by any means, or stored in
a database or retrieval system, without the prior written permission of the publisher.
0-07-150967-4
The material in this eBook also appears in the print version of this title: 0-07-147185-5.
All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after
every occurrence of a trademarked name, we use names in an editorial fashion only, and to the ben-
efit of the trademark owner, with no intention of infringement of the trademark. Where such desig-
nations appear in this book, they have been printed with initial caps.
McGraw-Hill eBooks are available at special quantity discounts to use as premiums and sales pro-
motions, or for use in corporate training programs. For more information, please contact George
Hoare, Special Sales, at or (212) 904-4069.
TERMS OF USE
This is a copyrighted work and The McGraw-Hill Companies, Inc. (“McGraw-Hill”) and its licen-
sors reserve all rights in and to the work. Use of this work is subject to these terms. Except as per-
mitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you

may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works
based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it
without McGraw-Hill’s prior consent. You may use the work for your own noncommercial and per-
sonal use; any other use of the work is strictly prohibited. Your right to use the work may be termi-
nated if you fail to comply with these terms.
THE WORK IS PROVIDED “AS IS.” McGRAW-HILL AND ITS LICENSORS MAKE NO
GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETE-
NESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY
INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR
OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED,
INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR
FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill and its licensors do not warrant or guar-
antee that the functions contained in the work will meet your requirements or that its operation will
be uninterrupted or error free. Neither McGraw-Hill nor its licensors shall be liable to you or any-
one else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages
resulting therefrom. McGraw-Hill has no responsibility for the content of any information accessed
through the work. Under no circumstances shall McGraw-Hill and/or its licensors be liable for any
indirect, incidental, special, punitive, consequential or similar damages that result from the use of
or inability to use the work, even if any of them has been advised of the possibility of such dam-
ages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or
cause arises in contract, tort or otherwise.
DOI: 10.1036/0071471855
We hope you enjoy this
McGraw-Hill eBook! If
you’d like more information about this book,
its author, or related books and websites,
please click here.
Professional
Want to learn more?
To my wife, Beth, and our children Melanie, Jeffrey, and David, for their

support and patience during the writing and revision of this text, and to
my parents, Nettie and David, for their emphasis on education and the
pursuit of knowledge.
—RMK
To Sally Ling, M.D., an incredibly hard working and considerate person
whom I am lucky enough to call my wife. She has given us three great
kids, Carolyn, Tyler, and Robert who keep me on my toes, and to my
mother and my father who always encouraged “the boys” to do our best.
—GCE
This page intentionally left blank
Student Reviewers
Jonathan Carnell
University of Kansas, School of Medicine
Class of 2009
Michael Curley
University of Wisconsin
School of Medicine and Public Health
Class of 2007
Nathan Heckerson
University of Kansas, School of Medicine
Class of 2009
Alicia K. Morgans
University of Pennsylvania, School of Medicine
Class of 2006
Andrew Schlachter
University of Kansas, School of Medicine
Class of 2009
This page intentionally left blank
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv
Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii
High-Yield Facts
Embryology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Histology and Cell Biology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Neural Pathways. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Anatomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Embryology: Early and General
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Cell Biology: Membranes
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Cell Biology: Cytoplasm
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
Cell Biology: Intracellular Trafficking
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Cell Biology: Nucleus
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
ix
For more information about this title, click here
Epithelium
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Connective Tissue
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181

Specialized Connective Tissues: Bone and Cartilage
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
Muscle and Cell Motility
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Nervous System
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
Cardiovascular System, Blood, and Bone Marrow
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
Lymphoid System and Cellular Immunology
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Respiratory System
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
x Contents
Integumentary System
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
Gastrointestinal Tract and Glands
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
Endocrine Glands
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
Reproductive Systems
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359

Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Urinary System
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
Eye and Ear
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
Head and Neck
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Thorax
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
Contents xi
Abdomen
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514
Pelvis
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 531
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 546
Extremities and Spine
Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
Answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 588
Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
xii Contents
Preface
In this 3rd edition of Anatomy, Histology, and Cell Biology: PreTest Self-Assessment
and Review, a significant number of changes and improvements have been
made. This PreTest reviews all of the anatomical disciplines encompassing

early embryology, cell biology, histology of the tissues and organs, as well
as regional human anatomy of the head and neck, thorax, abdomen, pelvis,
extremities, and spine. This edition represents a comprehensive effort to
integrate the anatomical disciplines with clinical scenarios and cases. The
authors’ development of numerous clinical vignettes, integrating basic sci-
ence disciplines with clinical medicine, will benefit students enrolled in
medical schools with integrated curricula, as well as those students in dis-
cipline-based programs of study. The sections on cell biology and micro-
scopic anatomy have been updated to include important new knowledge in
Cell and Tissue Biology. There is also a greater focus on clinically-related
questions, problems, and scenarios. New and improved light micrographs
have been added and matching questions have been eliminated in favor of
multiple-choice questions in keeping with recent changes in USMLE for-
mat. This 3rd edition is designed to help students prepare for USMLE Step 1,
Subject Exams in Human Anatomy and Histology, and even USMLE Step 2
in which the NBME plans to add more Step 1 questions.
New for this 3rd edition is the addition of radiographs and MRIs.
These radiological methods have become an important part of medical
practice. It is imperative that students be able to recognize structures and
relationships as part of their radiological anatomy knowledge base.
An updated High-Yield facts section is provided to facilitate rapid
review of specific areas of Anatomy that are critical to mastering the diffi-
cult concepts of each subdiscipline: embryology, cell biology, histology of
tissues and organs, regional human (gross) anatomy, pathology, and a brief
review of neuroanatomical tracts.
xiii
Copyright © 2007 by The McGraw-Hill Companies, Inc. Click here for terms of use.
This page intentionally left blank
Introduction
Each PreTest Self-Assessment and Review allows medical students to compre-

hensively and conveniently assess and review their knowledge of a particular
medical school discipline, in this instance anatomy and cell biology. The 500
questions parallel the format and degree of difficulty of the questions found
on the United States Medical Licensing Examination (USMLE) Step 1.
Although the main emphasis of this PreTest is preparation for Step 1, the
book will be very beneficial for medical students during their preclinical
courses whether they are enrolled in a medical school with a problem-based,
traditional, or hybrid curriculum. This PreTest focuses on an interdiscipli-
nary approach incorporating numerous clinical scenarios so it will also be
extremely valuable for students preparing for USMLE Step 2 who need to
review their anatomical knowledge. Practicing physicians who want to hone
their basic science skills and supplement their knowledge base before
USMLE Step 3 or recertification will also find this book to be a good begin-
ning in their review process.
This book is a comprehensive review of early embryology, cell biology,
histology (tissue and organ biology), and human (gross) anatomy with some
neuroanatomical topics covered through cases that integrate neuroanatomi-
cal tract information with regional anatomy of the head and neck. In keep-
ing with the latest curricular changes in medical schools, as much as
possible, questions integrate macroscopic and microscopic anatomy with
cell biology, embryology, and neuroscience as well as physiology, biochem-
istry, and pathology. This PreTest begins with early embryology, including
gametogenesis, fertilization, implantation, the formation of the bilaminar
and trilaminar embryo, and overviews of the embryonic and fetal periods.
This first section is followed by a review of basic cell biology, with separate
chapters on membranes, cytoplasm, intracellular trafficking, and the
nucleus. There are questions included to review the basics of mitosis and
meiosis as well as regulation of cell cycle events. Tissue biology is the third
section of the book, and it encompasses the tissues of the body: epithelium,
connective tissue, specialized connective tissues (cartilage and bone), mus-

cle, and nerve. Organ biology includes separate chapters on respiratory,
integumentary (skin), digestive (tract and associated glands), endocrine,
urinary, and male and female reproductive systems, as well as the eye and
the ear. The topics in tissue and organ histology and cell biology include
light and electron microscopic micrographs of appropriate structures that
xv
Copyright © 2007 by The McGraw-Hill Companies, Inc. Click here for terms of use.
students should be able to identify. The last section of the book contains
questions reviewing the basic concepts of regional anatomy of the head and
neck, thorax, abdomen, pelvis, and extremities. For each section, appropri-
ate x-rays, including MRIs, are included to assist the student in reviewing
pertinent radiological aspects of the anatomy. Where possible, information
is integrated with development and histology of the organ system.
Each multiple-choice question in this book contains four or more pos-
sible answer options. In each case, select the ONE BEST ANSWER to the
question.
Each question is accompanied by an answer, a detailed explanation,
and a specific page reference to an appropriate textbook. A bibliography
listing sources can be found following the last chapter of this PreTest.
xvi Introduction
Acknowledgments
The authors express their gratitude to their colleagues who have greatly
assisted them by providing light and electron micrographs as well as con-
structive criticism of the text, line drawings, and micrographs. They also
acknowledge Eileen Roach for her painstaking care in the preparation of
photomicrographs. Thanks to Drs. Amy Klion, Ann Dvorak, Anne W.
Walling, Christopher Maxwell, Dale R. Abrahamson, Daniel Friend, David A.
Sirois, David F. Albertini, Don W. Fawcett, Erik Dabelsteen, George Varghese,
Giuseppina Raviola, H. Clarke Anderson, J.E. Heuser, John K. Young, Julia
Neperud, K. Hama, Kristin M. Leiferman, Kuen-Shan Hung, Louis Wetzel,

Michael J. Werle, Nancy E.J. Berman, Per-Lennart Westesson, Robert P.
Bolender, Ronal R. MacGregor, Stanley L. Erlandsen, WenFang Wang,
Wolfram Sterry, and Xiaoming Zhang for their contribution of micro-
graphs and ideas for question development. Also, thanks to the Jeffrey
Modell Foundation and The Primary Immunodeficiency Resource Center
for use of the Martin Causubon case. The authors remain indebted to their
students and colleagues at the University of Kansas Medical Center, past
and present, who have challenged them to continuously improve their
skills as educators.
—RMK
—GCE
xvii
Copyright © 2007 by The McGraw-Hill Companies, Inc. Click here for terms of use.
This page intentionally left blank
1
High-Yield Facts
Embryology
Embryological development is divided into three periods:
The Prenatal Period consists of gamete formation and maturation, end-
ing in fertilization.
The Embryonic Period begins with fertilization and extends through the
first 8 weeks of development. It includes implantation, germ layer for-
mation, and organogenesis. This is the critical period for susceptibility to
teratogens.
The Fetal Period extends from the third month through birth.
THE PRENATAL PERIOD
The development of gametes begins with the duplication of chromosomal
DNA followed by two cycles of nuclear and cell division (meiosis).
Genetic variability is assured by crossing over of DNA, random
assortment of chromosomes, and recombination during the first meiotic

division. Errors can result in duplication or deletion of all or part of a spe-
cific chromosome.
Spermatogenesis
The process of spermatogenesis is continuous after puberty and each cycle
lasts about 2 months.
Spermatogonia in the walls of the seminiferous tubules of the testes
undergo mitotic divisions to replenish their population and form a group
of spermatogonia that will differentiate to form spermatocytes.
Primary spermatocytes are spermatogenic cells that have duplicated their
DNA (4N) and enter meiosis.
Secondary spermatocytes result from the first meiotic division (2N).
Spermatids are formed by the second meiotic division (1N).
Spermiogenesis
During this phase, spermatids mature into sperm by losing extraneous cyto-
plasm and developing a head region consisting of an acrosome (specialized
secretory granule) surrounding the nuclear material and grow a tail.
Copyright © 2007 by The McGraw-Hill Companies, Inc. Click here for terms of use.
Oogenesis
Oogenesis begins in the fetal period in females and is a discontinuous
process involving mitosis, meiosis, and maturation.
Oogonia undergo mitotic division and duplicate their DNA to form pri-
mary oocytes, but stop in the prophase of the first meiotic division until
puberty.
The second meiotic division is not concluded until fertilization occurs.
Maturational events include retention of protein synthetic machinery in
the surviving oocyte, formation of cortical granules that participate in
events at fertilization, and development of a protective glycoprotein coat, the
zona pellucida.
Fertilization
Fertilization occurs when sperm and oocyte cell membranes fuse. Follow-

ing coitus, exposure of sperm to the environment of the female reproduc-
tive tract causes capacitation, removal of surface glycoproteins and
cholesterol from the sperm membrane, enabling fertilization to occur.
Fusing of the first sperm initiates the zona reaction. Release of corti-
cal granules from the acrosome causes biochemical changes in the zona
pellucida and oocyte membrane that prevent polyspermy.
EMBRYONIC DEVELOPMENT
The embryo forms one germ layer during each of the first 3 weeks.
During the second week, the blastocyst differentiates into two germ layers,
the epiblast and the hypoblast. This establishes the dorsal
(epiblast)–ventral (hypoblast) body axis.
During the third week, the process of gastrulation occurs by which epiblast
cells migrate toward the primitive streak and ingress to form the endo-
derm and mesoderm germ layers below the remaining epiblast cells
(ectoderm).
Lateral body folding at the end of the third week causes the germ layers to
form three concentric tubes with the innermost layer being the endo-
derm, the mesoderm in the middle, and the ectoderm on the surface.
GERM LAYER DERIVATIVES
Mesoderm Derivatives
The mesoderm is divided into four regions (from medial to lateral): axial,
paraxial, intermediate, and lateral plate.
2 Anatomy, Histology, and Cell Biology
Axial mesoderm is located in the midline and forms the notochord.
Paraxial mesoderm forms somites. Somites are divided into sclerotomes
(bone formation), myotomes (muscle precursors), and dermatomes
(precursor of dermis).
Intermediate mesoderm gives rise to components of the genitourinary system.
Lateral plate mesoderm forms bones and connective tissue of the limbs
and limb girdles (somatic layer, also known as somatopleure) and the

smooth muscle lining viscera and the serosae of body cavities (splanch-
nic layer, also known as splanchnopleure).
Intermediate mesoderm is not found in the head region, and the lateral
plate mesoderm is not divided into layers there.
High-Yield Facts 3
Epithelium of skin (superficial epidermis layer)
Ectodermal All nervous tissue: formed by neuroectoderm:
Derivatives Brain and spinal cord (neural tube)
Peripheral nerves and other neural crest derivatives
The gastrointestinal tract
Organs that form as buds from
Epithelial the endodermal tube:
Endodermal linings of: Pharyngeal gland derivatives*
Derivatives Respiratory system
Digestive organs (liver, pancreas)
Terminal part of urogenital systems
Hypoblast Endoderm: Gametes migrate to gonads
All connective General connective tissue
tissue
†
Cartilage and bone
Mesodermal Blood cells (red and white)
Derivatives All muscle types: Cardiac, skeletal, smooth
Body cavities
Some organs:
Epithelial linings of: Cardiovascular system
Reproductive and urinary
systems (most parts)
*Pharyngeal derivatives: palatine tonsils, thymus, thyroid, parathyroids.
†

Some connective tissue in the head are derived from neural crest.
GERM LAYER DERIVATIVES
Ectoderm Derivatives
Formation of the primitive central nervous system is induced in the ecto-
derm layer by cells forming the notochord in the underlying mesoderm.
The neural plate ectoderm (neuroectoderm) forms two lateral folds
that meet and fuse in the midline to form the neural tube (neurulation).
Cells from the tips of the folds (neural crest) migrate throughout the
body to form many derivatives including the peripheral nervous system.
FORMATION OF THE HEAD REGION
Neural crest contributes significantly to formation of connective tissue ele-
ments in the head.
The bony skeleton of the head is comprised of the viscerocranium and
the neurocranium.
The neurocranium (cranial vault) is composed of a base formed by endo-
chondral ossification (chondrocranium) and sides and roof bones
formed by intramembranous ossification.
The chondrocranium is derived from both somitic mesoderm (occipital)
and neural crest.
The viscerocranium (face) is derived from the first two pharyngeal
(branchial) arches (neural crest in origin).
LIMB FORMATION
The limbs form as ventrolateral buds under the mutual induction of ecto-
derm [apical ectodermal ridge (AER)] and underlying mesoderm begin-
ning in the fifth week. The AER influences proximal-distal development.
Somatic lateral plate mesoderm (somatopleure) forms the bony and
connective tissue elements of the limbs and limb girdles while skeletal
muscle of the appendages is derived from somites.
Cranio-caudal polarity is determined by specialized mesoderm cells
[zone of polarizing activity (ZPA)] that release inducing signals such as

retinoic acid.
Homeobox genes are the targets of induction signals. They are named
after their homeodomain called the homeobox which is a DNA-binding
motif. Homeobox genes encode trancription factors that regulate processes
such as segmentation and axis formation.
Rotation of the limb buds establishes the position of the joints, the loca-
tion of muscle groups, and the pattern of sensory innervation (dermatome
map).
4 Anatomy, Histology, and Cell Biology
MATURATION OF THE CENTRAL NERVOUS SYSTEM
Both neurons and glia develop from the original neurectoderm forming the
neural tube.
Microglia are the exception: they develop from the monocyte-macrophage
lineage of mesodermal (bone marrow) origin and migrate into the CNS.
Induction of regional differences in the developing CNS is regulated
by retinoic acid (vitamin A). Overexposure of the cranial region to retinoic
acid can result in “caudalization,” i.e., development more similar to the
spinal cord.
During development, the spinal cord and presumptive brainstem
develop three layers: (1) a germinal layer or ventricular zone, (2) an
intermediate layer containing neuroblasts and comprising gray matter,
and (3) a marginal zone containing myelinated fibers (white matter).
Other layers are added in the cerebrum and cerebellum by cell migra-
tion along glial scaffolds.
The notochord induces the establishment of dorsal-ventral polarity
in the neural tube. Ventral portions of the tube will become the basal plate
and give rise to motor neurons, whereas the dorsal portions become the
alar plates, derivatives of which subserve sensory functions.
Meninges are formed by mesoderm surrounding the neural tube with
contributions to the arachnoid and pia from neural crest.

Defects in the CNS may result from several causes including high mater-
nal blood glucose levels and vitamin A overexposure and often involve bony
defects (e.g., spina bifida and anencephaly). Defects are most common in the
regions of neuropore closure. Folic acid, also known as folate, is a B-vitamin
that can be found in some enriched foods and vitamin supplements.Women
who take folate before pregnancy have a decreased risk of neural tube defects
(NTDs) including spina bifida and anencephaly. The U.S. Public Health Ser-
vice recommends that all women who could possibly become pregnant get
400 µg (or 0.4 mg) of folic acid every day. This could prevent up to 70% of
NTDs. Folic acid is found in some foods, such as enriched breads, pastas,
rice, and cereals (some with 100% of the daily requirement).
Fetal alcohol syndrome (FAS) is the most common cause of mental
retardation; FAS includes the triad of growth retardation, characteristic facial
dysmorphology and neurodevelopmental abnormalities. Alcohol rapidly
crosses the placenta and the fetal blood-brain barrier. Damage is dependent
on gestational age, alcohol dosage, and pattern of maternal alochol abuse.
Altered neural crest cell migration, differentiation and programmed cell death
High-Yield Facts 5