Development of the Tetrapod Limb.pptx

Development of the Tetrapod Limb
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1. Development of the Tetrapod Limb Presented by :- lovyansh lifescience

2. The vertebrate limb is an extremely complex organ with an asymmetrical arrangement of parts. The positional information needed to construct a limb has to function in a three-dimensional* coordinate system: The first dimension is the proximal-distal axis ("close-far"; shoulder-finger or hip-toe). The second dimension is the anterior-posterior axis (thumb-pinkie). • Finally, limbs have a dorsal-ventral' axis: our palms (ventral) are readily distinguishable froru our knuckles (dorsal). Three-dimensional coordinate system

3. Emergence of the limb bud. Proliferation of mesenchymal cells (arrows) from the somatic region of the lateral plate mesoderm causes the limb bud in the amphibian embryo to bulge outward. These cells generate the skeletal elements of the limb. Contributions of myoblasts from the lateral myotome provide the limb's musculature Formation of the Limb Bud

4. When mesenchyme cells enter the limb field, they secrete Fgf10that induces the overlying ectoderm to form a structure called the apical ectodermal ridge, or AER The AER runs along the distal margin of the limb bud and will become a major signaling center for the developing limb The apical ectodermal ridge

5. (1) maintaining the mesenchyme beneath it in a plastic, proliferating state that enables the linear (proximal-distal, shoulder-finger) growth of the limb; (2) maintaining the expression of those molecules that generate the anterior-posterior (thumb-pinkie) axis. (3) interacting with the proteins specifying the anterior-posterior and dorsal-ventral (knuckle-palm) axes so that each cell is given instructions on how to differentiate. Its roles of The apical ectodermal ridge

6. (A) Fgf10 expression is first seen throughout the lateral plate mesoderm. It becomes stabilized by Wnt8c to the area where hind limbs form. (B) Fgf10 synthesis is stabilized by the actions of Wntlb to the region where the forelimbs will form. (C) Fgf10 from these two regions of lateral plate mesoderm induces Fgf8 in the apical ectodermal ridge (AER). This induction is accomplished through a pathway involving Wnt3a in the responding ectoderm. Fgf8 secreted from the AER induces the continued mesodermal expression of Fgf10. The roles of Fgf8 in the intermediate mesoderm in inducing or maintaining Wnt expression are uncertain. Molecular model for initiation of the limb bud in the chick

7. The mesodermal cells that give rise to a vertebrate limb can be identified by (1) removing certain groups of cells and observing that a limb does not develop in their absence (2) transplanting groups of cells to a new location and observing that they form a limb in this new place (3) marking groups of cells with dyes or radioactive precursors and observing that their descendants partake in limb development. Specification of the limb fields

8. . (A) In situ-hybridizations show that during normal chick development, Tbx5 is found in the anterior lateral plate mesoderm, whileTbx4 is found in the posterior lateral plate mesoderm. Tbx5-containing limb buds produce wings/ while Tbx4-containing limb buds generate legs. (B) If a new limb bud is induced with an FGF- sccreting bead, the type of limb formed depends on which Tbx gene is expressed in the limb bud. If placed between the regions of Tbx4 and Tbx5 expression, the bead will induce the expression of Tbx4 posteriorly and Tbx5 anteriorly. The resulting limb bud will also express Tbx5 anteriorly and Tbx4 posteriorly and will generate a chimeric limb. (C) Expression of Tbx5 in the forelimb (w, wing) buds and in the anterior portion of a limb bud induced by an FGF-secreting bead. (The somite level can be determined by staining for Mrf4 mRNA, which is localized to the myotomes .) (D) Expression of Tbx4 in the hindlimb buds and in the posterior portion of an FGF- incluced limb bud. ( E,F) A chimeric limb induced by an FGF bead contains anterior wing structures and posterior leg structures. (F) is at a later developmental stage, after feathers form. Specification of limb t ype in the chick by Tbx4 and Tbx5.

9. The proximal-distal growth and differentiation of the limb bud are made possible by a series of interactions between the AER and the limb bud mesenchyme directly beneath it. This distal mesenchyme is called the progress zone (PZ) mesenchyme (and sometimes the undifferentiated zone), since its proliferative activity extends the limb bud. the structures of the extra set of digits are mirror images of the normally produced structures. The polarity has been maintained , but the information is now coming from both an anterior and a posterior direction. Thus this region of the mesoderm has been called the zone of polarizing activity (ZPA). SONIC HEDGEHOG DEFINES THE ZPA The zone of polarizing activity

10. When a ZPA is graphted 10 anterior limb bud mesoderm, duplicated digits emerge as a mirror image of the normal digits

11. Deletion of limb bone elements by the deletion of paralogous Hox genes. Hox gene patterning of the forelimb. Hox9 and Hox 10 paralogues specify the humerus , and Hox l0 paralogues are expressed to a lesser extent in the zeugopod . Hox11 paralogues are chiefly responsible for patterning the zeugopod Hox 12 paralogues function in the wrist, with a little patterning of the autopod ; and the Hox 13 paralogue group functions in the autopod . Hox gene specification

12. In addition to the interdigital necrotic zone , divided the limb digits . three other regions of the limb are "sculpted" by cell death. The ulna and radius are separated from each other by an interior necrotic zone , and two other regions, the anterior and posterior necrotic zones , further shape the end of the limb & seprated of anterior & posterior part of limb . Necrotic zone followed by cell death

13. The signal for apoptosis in the autopod is probably provided by the BMP proteins. BMP2, BMP4, and BMP7 are each expressed in the interdigital mesenchyme, and blocking BMP signaling (by infecting progress zone cells with retroviruses carrying dominant negative BMP receptors) prevents interdigital apoptosis; Since these BMPs are expressed throughout the progress zone mesenchyme, it is thought that cell death would be the "default" state unless there were active suppression of the BMPs. This suppression may come from the Noggin protein, which is made in the developing cartilage of the digits and in the perichondrial cells surrounding it If Noggin is expressed throughout the limb bud, no apoptosis is seen. Bmp signal for apoptosis

14. Possible involvement of BMPs in stabilizing cartilage and apoptosis