Tetrapod Limb Development

Similar documents
Tetrapod Limb Development

Tetrapod Limb Development

Vertebrate Limb Patterning

Development of the Axial Skeleton and Limbs. Professor Alfred Cuschieri Department of Anatomy University of Malta

Chapter 2. Genetic interaction between Gli3 and Alx4 during limb and craniofacial development CH Utrecht, The Netherlands

BIOL 4260 Human Evolu3onary Anatomy Lecture 12: Limb Development. Lecture 2: Fossil Record

Regionalization of the nervous system. Paul Garrity 7.68J/9.013J February 25, 2004

Bio Section IV Late Development. Development of the Tetrapod Limb. Pattern Formation. Skeletal pattern formation. Gilbert 9e Chapter 13

A New Vocabulary. Secreted Factors. Three Axes of Limb Development 11/9/15. Proteins released from a cell into surrounding area Examples

The chick oligozeugodactyly (ozd) mutant lacks sonic hedgehog function in the limb

Week 14. Development of the Musculoskeletal System

Positional signalling and the development of the humerus in the chick limb bud

Research Article: Veterinary Anatomy Case Report A case of polydactyly in the hind-limbs of a West African Dwarf goat in South-West Nigeria

Branching morphogenesis of the lung: new molecular insights into an old problem

Amber Kathleen O Connor. Bradley K Yoder, MENTOR Rosa Serra Robert A. Kesterson Jianbo Wang Stuart J. Frank A DISSERTATION

Gene Expression in the limbless Mutant: Polarized Gene Expression in the Absence of Shh and an AER

DEVELOPMENT. Lia Panman 1,2, *,, Antonella Galli 1, *, Nadege Lagarde 1, Odysse Michos 1, Gwen Soete 2,, Aimee Zuniga 1, and Rolf Zeller 1,

CONGENITAL HAND DIFFERENCES

Names: Block: Date: Building an Articulated Model of the Hand

Current Model for how cells become neural. Double Inhibition Model for Neural fate. Neural Development. How do cells become neurons?

Polarity and Segmentation. Chapter Two

CNS Developmental. Anke van Eekelen, PhD. Telethon Institute for Child Health Research

CHAPTER 8 LECTURE OUTLINE

Presidency General Hospital, Calcutta

a) They are the most common cause of pediatric kidney failure. b) They are always symptomatic. c) They can be asymmetric.

Uncoupling Sonic Hedgehog Control of Pattern and Expansion of the Developing Limb Bud

Patterning the Embryo

An unusual case of radial polydactyly, (tetraplication of the thumb, duplication of the radial carpal bones and bifurcation of the radius)

Principles of Anatomy and Physiology

Skeletal System. Prof. Dr. Malak A. Al-yawer Department of Anatomy/Embryology Section

THE SKELETAL SYSTEM. Focus on the Pectoral Girdle

SHHS Gen Bio Muscular System Lab

Relationship between retinoic acid and sonic hedgehog, two polarizing signals in the chick wing bud

Neuroepithelial Cells and Neural Differentiation

Hand Anatomy A Patient's Guide to Hand Anatomy

Biology 218 Human Anatomy

Developmental Biology

Segmentation. Serial Homology. Hox genes

Cholesterol Modification of Sonic Hedgehog Is Required for Long-Range Signaling Activity and Effective Modulation of Signaling by Ptc1

Name _ AP Biology Your Inner Fish not NOT DUE DATE: March 17, 2015

Developing Molecularly Targeted Therapies for Basal Cell Carcinoma. Ivor Caro, MD, FAAD

Axis Formation and Mesoderm Induction

Evidence that Shh cooperates with a retinoic acid inducible co-factor to establish ZPA-like activity

Lecture 1: Embryology of the Limbs (Development of Skeletal and Muscular Systems)

Interaction between the Signaling Molecules WNT7a and SHH during Vertebrate Limb Development: Dorsal Signals Regulate Anteroposterior Patterning

Supporting Information

Formation of Proximal and Anterior Limb Skeleton Requires Early Function of Irx3 and Irx5 and Is Negatively Regulated by Shh Signaling

Appendix chapter 3: Pterosaurs from the Lower Cretaceous of Brazil in the Stuttgart Collection (and supplement)

How is digit identity determined during limb development?

Dr.Israa H. Mohsen. Lecture 5. The vertebral column

DBio ypmental. Hensen's node, but not other biological signallers, can induce supernumerary digits in the developing chick limb bud

Developmental Biology

Chapter 8. The Pectoral Girdle & Upper Limb

RADIOGRAPHY OF THE WRIST

An Introduction to the Appendicular Skeleton

Pbx1/Pbx2 requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and Shh expression

evolution and development of primate teeth

Radiographic Positioning Summary (Basic Projections RAD 222)

RADIOGRAPHY OF THE HAND, FINGERS & THUMB

The Skeletal System THE APPENDICULAR SKELETON

Anatomy. Anatomy deals with the structure of the human body, and includes a precise language on body positions and relationships between body parts.

The skeleton consists of: Bones: special connective tissue, hard. Cartilage: special connective tissue, less hard than bones. Joints: joint is the

Figure 1: Bones of the upper limb

Lab Activity 11: Group II

EVO-DEVO: Evolution of animal design Lecture 4

University of Cape Town

Biceps Brachii. Muscles of the Arm and Hand 4/4/2017 MR. S. KELLY

Humerus. Ulna. Radius. Carpals

ARM Brachium Musculature

Sports Medicine Part I : ANATOMY OF THE SPINE, ABDOMEN AND SHOULDER COMPLEX

BRAIN DEVELOPMENT I: ESTABLISHMENT OF BASIC ARCHITECTURE. Thomas Marino, Ph.D.

Hands PA; Obl. Lat.; Norgaard s Thumb AP; Lat. PA. PA; Lat.: Obls.; Elongated PA with ulnar deviation

10/12/2010. Upper Extremity. Pectoral (Shoulder) Girdle. Clavicle (collarbone) Skeletal System: Appendicular Skeleton

SWGFAST Glossary - Anatomy

Koryo Hand Acupuncture Therapy

forearm posterior compartment

The role of HoxA11 and HoxA13 in the evolution of novel fin morphologies in a representative batoid (Leucoraja erinacea)

Wrist and Hand Anatomy

Report. Retinoic Acid Promotes Limb Induction through Effects on Body Axis Extension but Is Unnecessary for Limb Patterning

Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification

Anatomy and Physiology II. Review Shoulder Girdle New Material Upper Extremities - Bones

Muscles of the Upper Limb

Cell Birth and Death. Chapter Three

Hepatogenesis I Liver development

Retinoic acid in development and regeneration

Lecture IV. Mechanisms of Neural. Neural Development

Lecture 9: Forearm bones and muscles

Cover Page. The handle holds various files of this Leiden University dissertation

The Muscular System. Chapter 10 Part C. PowerPoint Lecture Slides prepared by Karen Dunbar Kareiva Ivy Tech Community College

Dynamic Changes in the Response of Cells to Positive Hedgehog Signaling during Mouse Limb Patterning

ROLE OF CANONICAL WNT-SIGNALLING IN JOINT FORMATION

Main Menu. Wrist and Hand Joints click here. The Power is in Your Hands

Skeletal System. Std. VIII

topographical anatomy

Polydactyly. A Review. Bev Guo, M.D., Steven K. Lee, M.D., and Nader Paksima, D.O., M.P.H. Classification. Embryology

Supplementary Figure 1. A microarray screen of organizers compared to non-organizer tissue reveals a putative organizer gene set.

Introduction to Human Osteology Chapter 3: Hands and Feet

10/10/2014. Structure and Function of the Hand. The Hand. Osteology of the Hand

A Patient s Guide to Adult Thumb Metacarpal Fractures

Pectoral (Shoulder) Girdle

Transcription:

Biology 4361 Developmental Biology Tetrapod Limb Development July 29, 2009

Tetrapod Limbs Merlin D. Tuttle Vicki Lockard and Paul Barry Father Alejandro Sanchez Anne Fischer

Limb Development - Overview Patterning Early development Specification Establishing limb axes Morphogenic models Cross-talk / regulation

Limb Patterning Humerus Carpals Metacarpals Dorsal Anterior Human arm Radius Ulna Phalanges Proximal Posterior Ventral Distal Chicken wing Knuckle Thumb Shoulder Finger Chicken leg Pinkie Palm Francesca V. Mariani and Gail R. Martin 2003 Nature 423:319-325 doi:10.1038/nature01655

Limb Field

Limb Bud Formation

Somites Vertebrate Limb Buds Hox5 Hox6 Limb bud Ectoderm Lateral plate mesoderm Mesodermal mesenchyme

Hoxc6 Specification of Limb Buds

Tbx Genes Specify Limb Type

Fgf/Wnt - Limb Bud Initiation

Limb Bud Axes Dorsal Anterior Proximal Distal Posterior Ventral

Apical Ectodermal Ridge Proximal-Distal Axis Apical Ectodermal Ridge (AER) forms at boundary between dorsal and ventral ectoderm lateral plate mesoderm Fgf10 Fgf10 Fgf8 Apical Ectodermal Ridge (AER)

Apical Ectodermal Ridge Manipulation

Progress Zone Fgf10 Progress Zone (PZ) Fgf8 Fgf4 AER establishes Progress Zone Fgf8 PZ ~200 μm Apical Ectodermal Ridge (AER)

Proximal Distal Proximal-Distal Specification Models Progress zone model: Identity established by residence time in PZ Early allocation and progenitor expansion: Elements specified early Specifying mechanism -??

Anterior-Posterior Specification Progress Zone (PZ) Morphogen Shh Apical Ectodermal Ridge (AER) Zone of Polarizing Activity (ZPA) Shh necessary and sufficient for establishing ZPA (NOTE Shh not necessary for polarity of styolpod) Shh induced by dhand and Hoxb8 ZPA maintained by feedback loop with AER

ZPA/AER Feedback Loop Model 1. dhand (transcription factor) and Fgf8 (from AER) stimulate Shh - Fgf8 (and Fgf4) maintains Shh expression 2. Shh up-regulates Gremlin1 in posterior mesenchyme - Grem1 antagonizes BMP ligands - BMPs repress Fgf expression in AER 3. Wnt7a maintains Shh Wnt7a determines the size of AER Loss-of-function mutants (both Shh and Grem1) = syndactyly, loss of digits

ZPA Morphogen Gradient 1 2 Shh gradient ZPA 5 3 4 High [Morphogen] Low 5 4 3 Posterior 2 Anterior

ZPA Transplantation Posterior tissue transplant to anterior = duplicated autopod Mirror-image duplication effects can be replicated by transplanting Shh bead Retinoic acid operates upstream of Shh - implant RA-soaked bead =mirror-image duplication 4 3 2 2 3 4 new posterior C. Tickle, Nature Molecular Biology 7(2006)45-53

Shh Specifies Digit Identity

Drosophila Drosophila Hedgehog Pathway Sonic hedgehog (vertebrates) Gli1, 2, 3 (vertebrates)

Vertebrate Hedgehog Activity Vertebrate homologues: Hh - Sonic hedgehog (Shh), plus others Ci Gli (Gli1, Gli2, Gli3) Without SHH: Gli3 proteolytic fragment acts as a transcriptional repressor (Gli3R) - represses e.g. dhand, Gremlin, Fgf4, Hoxd13 With SHH signal: Gli s retained in long form acts as a transcriptional activator - e.g. Gli1 activates Shh Gli3 -/- = polydactyly; (~)8 digits; unpatterned Shh -/- = 1 digit; Gli3R prevails Anterior high Gli3R Posterior low Gli3R SHH main function may be to relieve Gli3R repression in posterior region

Shh/Gli3 Knockouts Shh digit specification: 5,4 - autocrine 3 autocrine and diffusion (paracrine) 2 diffusion (paracrine) 1 not Shh-dependent Shh -/- Shh knockout one digit Shh -/- /Gli3 -/- Shh/Gli3 knockouts multiple digits #1 or unspecified variants

Hox Genes in Early Limb Bud Gli3 (repressor)

5 Hox Genes Pattern Limb Elements Forelimb Hindlimb

BMPs Regulate Digital Identity Shh initiates BMP2 and BMP7 gradients - BMPs in interdigital mesoderm specifies identity of digits anteriorly - BMP targets unknown NOTE Fgfs from AER control phalange development; Shh bead inserted between digits can add phalange; Shh sustains Fgf signal; Fgf inhibitor = lack of phalange Remove interdigital mesoderm Insert BMP antagonist into interdigital webbing Noggin BMP antagonist

Dorsal-Ventral Specification Dorsal Progress Zone (PZ) Ectoderm Apical Ectodermal Ridge (AER) Zone of Polarizing Activity (ZPA) Ventral Wnt7a necessary and sufficient to dorsalize limb bud - Wnt7a knockouts = ventral footpads on both surfaces - induces Lmx1 in dorsal mesenchyme - Lmx1 knockouts = ventralized phenotype

Apoptosis in Limb Primordia BMP signals

2024 © healthdocbox.com Privacy Policy | Terms of Service | Feedback