Editing Paracrine signaling (section)

====Aberrant JAK-STAT pathway and bone mutations====
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 [[Achondroplasia|achondroplasic]] dwarfism (viable).<ref name="Bonaventure,">{{cite journal |doi=10.1002/(SICI)1096-8628(19960503)63:1<148::AID-AJMG26>3.0.CO;2-N |title=Common mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for achondroplasia, hypochondroplasia, and thanatophoric dwarfism |year=1996 |last1=Bonaventure |first1=J. |last2=Rousseau |first2=F. |last3=Legeai-Mallet |first3=L. |last4=Le Merrer |first4=M. |last5=Munnich |first5=A. |last6=Maroteaux |first6=P. |journal=American Journal of Medical Genetics |volume=63 |pages=148–54 |pmid=8723101 |issue=1}}</ref> This is due to a mutation in a [[Fibroblast growth factor|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.<ref name="Shiang,">{{cite journal |doi=10.1016/0092-8674(94)90302-6 |title=Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia |year=1994 |last1=Shiang |first1=Rita |last2=Thompson |first2=Leslie M. |last3=Zhu |first3=Ya-Zhen |last4=Church |first4=Deanna M. |last5=Fielder |first5=Thomas J. |last6=Bocian |first6=Maureen |last7=Winokur |first7=Sara T. |last8=Wasmuth |first8=John J. |journal=Cell |volume=78 |issue=2 |pages=335–42 |pmid=7913883|s2cid=20325070 }}</ref>