Question

As children's arms and legs grow, cartilage in their arms and legs grows, stops growing, and then is replaced with bone. If the cartilage stops growing too early, the bones will be very short. Normally, the cartilage cells grow until they sense a signal called FGF3. A receptor tyrosine kinase called FGFR3 binds to FGF3 and begins a series of events inside the cartilage cells, including a phosphorylation cascade, that cause them to stop growing. Imagine there is a mutation in the FGFR3 gene that causes the protein to dimerize even when there is no FGF3. A. How will this mutation affect the amount of signals sent by FGFR3, and why? Justify your response (roughly 1-2 sentences). B. Given your answer for part A, how will this mutation affect the growth of the bones, and why? Explain. (roughly 1-2 sentences) C. What is a phosphorylation cascade, and how does it amplify signals? (Feel free to use a drawing, if you'd like, to support your explanation.) (roughly 2-3 sentences) D. Given your answer to part A, do you predict this mutation will be dominant or recessive? Justify your response. (roughly 1-2 sentences)

Answer 1

Step 1

The development of bones occurs by endochondral ossification and intramembranous ossification. The intramembranous ossification occurs in the bone of ribs and pelvis that develops from mesenchyme tissue. The long bones develop by endochondral ossification that involves cartilage replacement with the bones. This process occurs with the help of chondrocytes that undergoes hypertrophy. The bone invades the extracellular matrix secreted by the chondrocytes.

Step 2

The negative regulator for the development of long bones is FGFR3. It is a receptor tyrosine kinase that allows differentiation of the chondrocytes. The fibroblast growth factor 3 (FGF3) binds with the FGFR 3 and allows a cascade event that inhibits cartilage cell growth.

Step 3

Answer-

A. The mutation in the FGFR 3 gene allows the phosphorylation even in the absence of a signaling molecule, FGF 3. This causes an alteration in the growth plate chondrocytes hypertrophic differentiation and leads to achondroplasia.

B. This mutation leads to a short length of bones causing dwarfism. This occurs due to receptor, FGFR3 that is constitutively active and causes this condition.

C. The phosphorylation cascade is a process that allows phosphorylation of the next protein by the previous enzyme. This process allows phosphorylation of many proteins in a sequence one after another. The signal from the growth factor is amplified by cascades.