text: The JAK-STAT signaling pathway is instrumental in the development of limbs, specifically in its ability to regulate bone growth through paracrine signaling of cytokines. However, mutations in this pathway have been implicated in severe forms of dwarfism: thanatophoric dysplasia (lethal) and achondroplasic dwarfism (viable). This is due to a mutation in a Fgf gene, causing a premature and constitutive activation of the Stat1 transcription factor. Chondrocyte cell division is prematurely terminated, resulting in lethal dwarfism. Rib and limb bone growth plate cells are not transcribed. Thus, the inability of the rib cage to expand prevents the newborn's breathing.