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#regulatory factor

2 public questions tagged with this topic.

Limb Development -lll

Which factor plays a major role in regulating digit identity by controlling Sonic Hedgehog (Shh) expression?

Digit identity along anterior-posterior axis depends on graded Sonic Hedgehog from zone of polarizing activity. SHH induces Gremlin1, which antagonizes BMPs, thereby sustaining AER FGFs and forming SHH-Gremlin-FGF feedback loop that prolongs SHH exposure and expands progenitors. Higher and longer SHH promotes posterior digit fates through sustained Hoxd13 and Gli activator activity and repression of Gli3 repressor. Interruption of Gremlin alters SHH duration and range, changing digit number and morphology. TBX5 specifies forelimb field, BMP4 drives apoptosis, Wnt3a induces AER.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: ZPA SHH-Gremlin loop and digit identity.

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Cell Cycle Regulation

Which regulatory factor is crucial for the metaphase-to-anaphase transition?

Metaphase to anaphase transition represents irreversible commitment executed by APC/C bound to Cdc20 coactivator. Throughout prometaphase chromosomes attach via kinetochores, generating unattached kinetochore signal converting Mad2 to active inhibitor forming mitotic checkpoint complex with BubR1, Bub3, and Cdc20 that binds APC/C core to block E2 recruitment. Upon achievement of biorientation of all chromosomes and establishment of tension, checkpoint protein recruitment stops, complex disassembles, and free Cdc20 associates with phosphorylated APC/C previously primed by CDK1 and Plk1. Active APC/C-Cdc20 polyubiquitinates securin and cyclin B with K11 chains for proteasomal destruction. Securin normally binds and locks separase protease in inactive conformation together with cyclin B-CDK1 phosphorylation. Degradation liberates separase that cleaves kleisin Rad21 subunit of cohesin ring embracing sister chromatids since S phase, opening ring, while cyclin B destruction drops CDK1 activity permitting phosphatase activation and mitotic exit. Blocking securin degradation prevents chromatid separation. This circuitry is highly conserved across eukaryotes, integrating growth factor signals, DNA damage surveillance, and developmental cues, and its disruption frequently underlies oncogenesis, providing targets for checkpoint inhibitors and cancer therapeutics.

Ref: Peters et al., Cell 1998, APC/C Regulation. Musacchio, Nat Rev Mol Cell Biol 2011, Anaphase.

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