RhoA signaling and modulation of actin polymerization also regulates Sox9 expression via controlling transcriptional Sox9 activity. The expression and transcriptional activity of Sox9 is directly linked with the loss of RhoA activity and illustrates how RhoA participates in the transcriptional control of specific protein expression. RhoA as well as several other members of the Rho family are identified as having roles in the regulation of the cytoskeleton and cell division. RhoA plays a pivotal role in G1 cell cycle progression, primarily through regulation of cyclin D1 and cyclin-dependent kinase inhibitors (p21 and p27) expression. These regulation pathways activate protein kinases, which subsequently modulate transcription factor activity. RhoA specifically suppresses p21 levels in normal and transformed cell lines via a p53-independent transcriptional mechanism while p27 levels are regulated using effector Rho-associated kinases. Cytokinesis is defined by actomyosin-based contraction. RhoA-dependent diaphanous-related formins (DRFs) localize to the cleavage furrow during cytokinesis while stimulating local actin polymerization by coordinating microtubules with actin filaments at the site of the myosin contractile ring. Differences in effector binding distinguish RhoA amongst other related Ras homologs GTPases. Integrins can modulate RhoA activity depending on the extracellular matrix composition and other relevant factors. Similarly, RhoA's stimulation of PKN2 kinase activity regulates cell-cell adhesion through apical junction formation and disassembly. Though RhoA is most easily recognized from its unique contributions in actin-myosin contractility and stress fiber formation, new research has also identified it as a key factor in the mediation of membrane ruffling, lamellae formation and membrane blebbing. A majority of this activity occurs in the leading edge of cells during migration in coordination with membrane protrusions of breast carcinoma. Molecules act on various receptors, such as NgR1, LINGO1, p75, TROY and other unknown receptors (e.g. by CSPGs), which stimulates RhoA. RhoA activates ROCK (RhoA kinase) which stimulates LIM kinase, which then inhibits cofilin, which effectively reorganizes the actin cytoskeleton of the cell. In the case of neurons, activation of this pathway results in growth cone collapse, therefore inhibits the growth and repair of neural pathways and axons.