1 / 22

Limb Patterning: Proximal-Distal Axis

Limb Patterning: Proximal-Distal Axis. Gilbert - Chapter 16 Do you want to hear a talk from an ASTRONAUT 4/17??. Today’s Goals. Become familiar with several aspects of limb formation in the tetrapod Limb initiation Forelimb vs. hindlimb Where to make a limb? Limb patterning

cleave
Download Presentation

Limb Patterning: Proximal-Distal Axis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Limb Patterning: Proximal-Distal Axis Gilbert - Chapter 16 Do you want to hear a talk from an ASTRONAUT 4/17??

  2. Today’s Goals • Become familiar with several aspects of limb formation in the tetrapod • Limb initiation • Forelimb vs. hindlimb • Where to make a limb? • Limb patterning • Dorsal/ventral • Anterior/Posterior • Proximal/distal

  3. Generating Limb Axes • Classical embryonic manipulations from the dating from the 1940’s • John Saunders • Series of surgical rearrangements that later became the basis for what we know about molecular signals in limb formation • He identified specialized areas in the limb that were necessary for development of the different axes

  4. John Saunders

  5. Proximal Distal Axis • Growth along P-D axis made possible by interaction between 2 tissues • Apical ectodermal ridge (AER) • Thickening of ectoderm at distal tip of limb bud • Very important for several aspects of limb formation • Progress zone (PZ) • Mesenchyme directly underneath AER • Proliferates to lengthen the limb bud

  6. PZ

  7. Experimental Manipulations • Remove AER at any time • Distal limb development ceases • Graft extra AER to existing limb • Extra distal structures form • CONCLUDE: • AER is necessary and sufficient for distal limb formation

  8. Removal of AER at different times: loss of various structures

  9. More Experimental Manipulations • Remove PZ from wing, replace it with leg PZ • Toes form at distal tip of wing! • Remove PZ from wing, replace with mesenchyme from non-limb • Limb development ceases, AER disappears • CONCLUDE: • PZ involved in specifying limb type • AER dependent on PZ to continue developing

  10. Overall conclusions: AER, PZ • AER required for distal limb development • AER keeps PZ in a proliferative state, and PZ sustains AER (feedback loop) • What molecules are involved in this interaction??

  11. FGFs and the AER • FGFs, including FGF10, FGF8 • Important in formation, sustaining the AER • FGF10 expression in the mesenchyme of the forming limb bud induces formation of AER in the overlying ectoderm • This occurs at the distal tip of the limb • FGF10 induces expression of FGF8 in AER • FGF8 is secreted from AER, signals to PZ to keep dividing • FGF8 acts in feedback loop to instruct PZ to maintain FGF10 expression

  12. FGF8 expression

  13. FGFs and The AER • If the AER is removed from the developing limb • Normally, development of distal limb ceases • BUT - if remove AER and put in a bead coated in FGF • NORMAL DEVELOPMENT OF LIMB!

  14. How are cells specified with regard to P-D axis? • The AER and PZ allow for limb outgrowth, but how do proximal cells know to form humerus, distal cells know to form digits? • 2 Models • Progress zone model • Early allocation and progenitor expansion model

  15. P-D axis specification: Guess who? • Regardless of which model for the P-D axis wins out . . . • Hox genes appear to be involved! • These genes are expressed in a nested pattern that changes during limb development • When mutations occur, changes can occur in the P-D axis

  16. Specific Hox Paralog groups are expressed in specific regions of the limb

  17. A= Wild Type Mouse; B = Hox a-11, Hox d11 double mutant mouse; C = Human Polysyndactyly (HomozygousHoxD13 mutation)

More Related