
@article {161134,
	title = {The patterning and proliferation roles of Shh are partitioned on distinct exosomes.},
	journal = {Dev Biol},
	volume = {528},
	year = {2025},
	month = {2025 Dec},
	pages = {239-254},
	abstract = {<p>Sonic hedgehog (Shh) is a pivotal morphogen in spinal cord development, orchestrating both ventral neural patterning and progenitor proliferation. How these distinct outcomes are specified has remained elusive. Here, we uncover that Shh is secreted via two biochemically and functionally distinct exosomal pools. A dense vesicle fraction, Shh-P150, drives Smoothened-Gli1 signalling to establish ventral progenitor identities, while a lighter pool, Shh-P450, activates a Smoothened-Gαi-dependent pathway that enhances progenitor proliferation without inducing ventral fate. We identify Rab7, a late endosomal regulator, as essential for Shh-P150 biogenesis and for notochord-mediated ventral neural patterning. Loss of Rab7 biases secretion toward the proliferative Shh-P450 pool and disrupts morphogenetic signalling. These findings establish exosomal packaging as a molecular switch that toggles Shh between its mitogenic and morphogenetic roles. By linking exosome biogenesis to developmental outcomes, our work reveals a novel mechanism that safeguards the balance between pattern formation and progenitor expansion during neural tube development, with implications for both developmental disorders and disease contexts where Shh signalling is misregulated.</p>
},
	keywords = {Animals, Body Patterning, Cell Proliferation, Exosomes, Gene Expression Regulation, Developmental, Hedgehog Proteins, Mice, Neural Tube, Notochord, rab GTP-Binding Proteins, rab7 GTP-Binding Proteins, Signal Transduction, Smoothened Receptor, Spinal Cord, Zinc Finger Protein GLI1},
	issn = {1095-564X},
	doi = {10.1016/j.ydbio.2025.09.017},
	author = {Walvekar, Ankita and Pandey, Shivangi and Kamat, Siddhesh S and Ladher, Raj K and Vyas, Neha}
}
@article {159724,
	title = {Role of Pcdh15 in the development of intrinsic polarity of inner ear hair cells.},
	journal = {PLoS Genet},
	volume = {21},
	year = {2025},
	month = {2025 Aug},
	pages = {e1011825},
	abstract = {<p>In vertebrates, auditory information is transduced in the cochlea by mechanosensory hair cells (HC) through an eccentrically organised structure known as the hair bundle. This consists of a true cilium, known as the kinocilium, and modified microvilli, known as stereocilia. The hair bundle has a distinct structure with stereocilia organised in graded rows, with the longest abutting the kinocilium. The hair bundles of all HC are aligned to the tissue axis and are planar polarised. Important in the development and physiology of HC are protein bridges consisting of cadherin-23 (CDH23) and protocadherin-15 (PCDH15). These link the tips of stereocilia, where they play a role in mechanotransduction, and between the kinocilia and the stereocilia, where they are involved in development. Both Cdh23 and Pcdh15 mutations result in defects in planar polarity; however, the mechanism through which this defect arises is unclear. Using a novel mutant for the Pcdh15-CD2 isoform, we show that while the initial deflection of the kinocilium occurs, its peripheral migration to register with Gαi is perturbed. Pcdh15-CD2 genetically interacts with Gpsm2, perturbing vestibular function. We find that the earliest expression of PCDH15-CD2 is at the base of the kinocilia, and the defects in morphogenesis occur before the formation of kinocilial links. By re-introducing functional PCDH15-CD2, we show that polarity can be restored. Our data suggest that, in addition to its adhesive role, PCDH15-CD2 has an early role in intrinsic hair cell polarity through a mechanism independent of kinocilial links.</p>
},
	keywords = {Animals, Basal Bodies, Cadherin Related Proteins, Cell Polarity, Ear, Inner, Gene Knock-In Techniques, Hair Cells, Auditory, Mice, Mutation, Phosphorylation, Protein Domains, Protein Precursors, Tyrosine},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1011825},
	author = {Kaushik, Raman and Pandey, Shivangi and Prakash, Anubhav and Ganatra, Fenil and Abe, Takaya and Kiyonari, Hiroshi and Ladher, Raj K}
}
