The mechanisms of vertebrate Hedgehog signaling are linked to the biology of the primary cilium, an antenna-like organelle that projects from the surface of most vertebrate cell types. Although the advantages of restricting signal transduction to cilia are often noted, the constraints imposed are less frequently considered, and yet they are central to how Hedgehog signaling operates in developing tissues. In this Review, we synthesize current understanding of Hedgehog signal transduction, ligand secretion and transport, and cilia dynamics to explore the temporal and spatial constraints imposed by the primary cilium on Hedgehog signaling in vivo.
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http://dx.doi.org/10.1242/dev.195552 | DOI Listing |
Dev Cell
January 2025
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:
Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
Department of Pharmaceutics and Drug Manufacturing, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo 11435, Egypt.
Background/objectives: Basal cell skin cancer (BCSC) develops when skin cells proliferate uncontrollably. Sonidegib (SDB) is a therapeutic option for the treatment of BCSC by inhibiting hedgehog signaling. The problems with SDB's low solubility, poor bioavailability, resistance, poor targeting, and first-pass action make it less effective when taken orally.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Biochemistry and Biophysics, "Carol Davila" University of Medicine and Pharmacy of Bucharest, 050474 Bucharest, Romania.
Cancer stem cells (CSC) are known to be the main source of tumor relapse, metastasis, or multidrug resistance and the mechanisms to counteract or eradicate them and their activity remain elusive. There are different hypotheses that claim that the origin of CSC might be in regular stem cells (SC) and, due to accumulation of mutations, these normal cells become malignant, or the source of CSC might be in any malignant cell that, under certain environmental circumstances, acquires all the qualities to become CSC. Multiple studies indicate that lifestyle and diet might represent a source of wellbeing that can prevent and ameliorate the malignant phenotype of CSC.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Developmental and Regenerative Biology, Medical Research Institute, Institute of Science Tokyo, Tokyo 113-8510, Japan.
The eye primordium of vertebrates initially forms exactly at the side of the head. Later, the eyeball architecture is tuned to see ahead with better visual acuity, but its molecular basis is unknown. The position of both eyes in the face alters in patients with holoprosencephaly due to () mutations that disturb the development of the ventral midline of the neural tube.
View Article and Find Full Text PDFCancers (Basel)
January 2025
School of Biotechnology, KIIT Deemed to Be University, Bhubaneswar 751024, India.
The complex signaling network within the breast tumor microenvironment is crucial for its growth, metastasis, angiogenesis, therapy escape, stem cell maintenance, and immunomodulation. An array of secretory factors and their receptors activate downstream signaling cascades regulating breast cancer progression and metastasis. Among various signaling pathways, the EGFR, ER, Notch, and Hedgehog signaling pathways have recently been identified as crucial in terms of breast cancer proliferation, survival, differentiation, maintenance of CSCs, and therapy failure.
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