The Role of Planar Cell Polarity Effector Gene Inturned in Hedgehog Signaling, Ciliogenesis, and Skeletal Development in Mammalian Embryogenesis
Open Access
- Author:
- Chang, Rachel
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Aimin Liu, Thesis Supervisor
Daniel J Cosgrove, Thesis Honors Advisor - Keywords:
- Hedgehog signaling
Indian Hedgehog signaling
Sonic Hedgehog signaling
planar cell polarity effector gene
polydactyly
primary cilia
ciliogenesis
Inturned
skeletal development
endochondral ossification - Abstract:
- The coordinated interactions of molecular and cellular components during embryonic development are highly dependent upon the core developmental pathways. Among these pathways is Hedgehog (Hh) signaling. Hh signaling affects a variety of developmental processes, including body axis formation, neural and digit patterning, gonad development, cell proliferation, and bone ossification and growth. In mammals, the primary cilia, microtubule-based organelles on the surface of quiescent cells, are required for Hh signaling. To further explore the genetic basis of embryogenesis, we examined the double-thumb (dtm) mouse mutant of the Inturned (Intu) gene, a planar cell polarity (PCP) effector gene. PCP effector genes function downstream of PCP genes that are responsible for processes such as convergent extension and alignment of cilia in the cochlea. Dtm mutants carry a recessive, missense point mutation in Intu that results in decreased body size and survival, skeletal defects (mild polydactyly with one extra digit per limb, reduced and delayed ossification in the limbs and vertebrae, and misaligned ribs and sternal vertebrae), delayed neural patterning, and reduced ciliation in the kidney and ventral node. By characterizing the expression of a Hh pathway target, Patched1 (Ptch1), we found that Hh signaling is decreased during cartilage differentiation. These results suggest that Intu is important for both Indian Hedgehog (Ihh)-mediated bone ossification and Sonic Hedgehog (Shh)-mediated embryonic patterning, likely through regulating cilia formation. Such investigations into the genetic and molecular basis of ciliogenesis and skeletal development may have future clinical applications in the understanding and treatment of cilia-related ailments in humans.