What happens when SHH is conditionally knocked out in the mouse limb?
Conditional deletion of Sonic hedgehog specifically in mouse limb mesenchyme after initiation eliminates posterior patterning signal essential for digit specification. Without SHH, Gli3 is fully processed to repressor throughout bud, causing oligodactyly, often single digit resembling thumb, reduced proliferation due to decreased Cyclin D1 expression, failure to maintain Gremlin1 leading to elevated BMP activity and enhanced apoptosis, premature decline of AER FGF8. Resultant limb exhibits truncated autopod with loss of posterior digits, demonstrating requirement of SHH for maintaining growth, survival, and anterior-posterior identity beyond early budding stage and regulating Erk signaling downstream.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: Conditional SHH knockout phenotype and digit loss in mouse.