Term
| Where do the limb buds arise? |
|
Definition
| Limb Buds Arise in the Somatic Layer of the Lateral-Plate Mesoderm |
|
|
Term
| What limb components derive from the ectoderm? |
|
Definition
| Epidermis & derivatives (hairs, nails, sweat & sebaceous glands) |
|
|
Term
| What limb components derive from the mesoderm? |
|
Definition
| dermis, connective tissue, tendons, cartilage, bone, & muscle |
|
|
Term
| What are the different types of molecular mechanisms for limb outgrowth? |
|
Definition
PROXIMODISTAL (Limb Outgrowth) ANTEROPOSTERIOR (Digit Specification) DORSOVENTRAL (AER Position, Muscle Pattern) |
|
|
Term
| What are the basics of the apical ectodermal ridge? |
|
Definition
Ectoderm at the distal border of the limb thickens and forms the ridge Induced by underlying mesenchyme Secretes FGF-8 & FGF-4 Maintains Progress Zone Required for limb-bud outgrowth |
|
|
Term
| What are the basics of the progress zone? |
|
Definition
population of undifferentiated rapidly proliferating cells adjacent to the AER Induced by AER Secretes FGF-10 Maintains AER Rapid cell division Inhibited differentiation Required for limb-bud outgrowth |
|
|
Term
| Explain the importance of Hoxd expression in limb-bud outgrowth |
|
Definition
Required for limb-bud outgrowth (Hox 11 knockout mice lack radius & ulna) Distal-to-proximal limb patterning corresponds to nested 5’-to-3’ expression of homeobox (Hoxd) genes. genetic specification of proximo-distal pattern - 5’-->3’ = posterior distal --> anterior proximal example - Hoxd13 is the most 5' gene and its expression is the most distal AER (FGF-4 & FGF-8) maintains Hoxd13 expression in PZ |
|
|
Term
| How does Hoxd differentiation work in limb outgrowth? |
|
Definition
Cells left behind by distally-growing PZ lose expression of 5’-HoxD genes and differentiate first. First cells left behind specify most proximal limb structures. Last to leave specify more distal limb structures. |
|
|
Term
| In digit specification what are the anterior and posterior ends develop into? |
|
Definition
Anterior --> Thumb Posterior --> Little finger |
|
|
Term
| What are the basics of the zone of polarizing activity? |
|
Definition
Located along posterior border of limb produces protein product of the Sonic Hedgehog gene (Shh) ZPA tissue grafted to anterior limb border induces mirror image limb-skeletal duplication Encodes posterior "positional information" |
|
|
Term
| Explain Sonic hedgehog (Shh) |
|
Definition
Normal product of zone of polarizing activity region Ectopic Shh expression induced by retinoic acid implants Skeletal duplication induced by Shh implants (both purified protein and implanted cells engineered to overexpress Shh protein) Shh induces FGF-4 secretion by apical ectodermal ridge (thus integrating proximodistal with anteroposterior patterning) Shh induces Hoxd expression |
|
|
Term
|
Definition
Involved in dorsoventral axis Restricted to dorsal ectoderm Induces Lmx1 in dorsal mesoderm Wnt7a knockouts fail to form AER |
|
|
Term
| Explain En1 gene expression |
|
Definition
Involved in dorsoventral axis Restricted to ventral ectoderm Inhibits r-fng in ventral ectoderm expressing Wnt7a - AER forms at the boundary of expression between En1 and Wnt7a |
|
|
Term
|
Definition
Fibroblast growth factor 8 involved in proximodistal growth located in entire AER maintains proliferation & inhibits differentiation in progress zone maintained by FGF-10 |
|
|
Term
|
Definition
fibroblast growth factor 4 involved in Proximodistal limb-bud outgrowth located in posterior AER maintains proliferation & inhibits differentiation in progress zone induced by Shh |
|
|
Term
|
Definition
fibroblast growth factor 10 involved Proximodistal limb-bud outgrowth located in progress zone maintains AER structure and function |
|
|
Term
| What is the function of retinoic acid? |
|
Definition
Low concentration Mimics ZPA induces Shh & Hox High concentration shuts down AER & PZ, stops outgrowth |
|
|
Term
| What is the function of Lmx1? |
|
Definition
involved in Dorsoventral axis located in the dorsal mesoderm induced by Wnt7a specifies dorsal structure |
|
|
Term
| What is the function of r-fng? |
|
Definition
involved in Dorsoventral axis inhibited by En1 in ventral ectoderm expressing Wnt7a (i.e., site of AER) |
|
|
Term
| What does the epithelium of the limb develop from? |
|
Definition
| Epithelium is Epidermis & derivatives (hairs, nails, glands, lining of blood vessels) derive from covering ectoderm |
|
|
Term
| What does the connective tissue of the arm develop from? |
|
Definition
| Connective Tissues: Dermis & Skeletal Tissues (tendons, ligaments, cartilage, bone) comes from somatic layer of lateral plate mesoderm |
|
|
Term
| What does the muscle of the limb develop from? |
|
Definition
| Skeletal Muscle develops from myotome of somites |
|
|
Term
| Where do the nerves of the upper limb come from? |
|
Definition
Dorsal & ventral branches of ventral primary rami. Follow and innervate peripherally migrating muscle masses |
|
|
Term
| How does the number of bones differ in the upper limb distally as opposed to proximally? |
|
Definition
| More bones distally (hand compared to upper arm for example) |
|
|
Term
| Explain the changes in position of limbs before birth |
|
Definition
At 5 weeks faster proliferation on the anterior side compared to the posterior causes lateral and caudal outgrowth At 6 weeks the limbs bend anteriorly so elbows and knees point laterally and palms and soles face the trunk At 7 weeks upper and lower limbs rotate 90 degrees about their long axes but in opposite directions, elbows point caudally and knees cranially At 8 weeks torsion of lower limbs results in twisted or "barber pole" arrangement of their cutaneous innervation |
|
|
