Ptch1 is essential for cochlear marginal cell differentiation and stria vascularis formation.

Qin, T ; So, KKH ; et al.

In: Cell reports, Jg. 43 (2024-04-23), Heft 4, S. 114083

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A common cause of deafness in humans is dysregulation of the endocochlear potential generated by the stria vascularis (SV). Thus, proper formation of the SV is critical for hearing. Using single-cell transcriptomics and a series of Shh signaling mutants, we discovered that the Shh receptor Patched1 (Ptch1) is essential for marginal cell (MC) differentiation and SV formation. Single-cell RNA sequencing analyses revealed that the cochlear roof epithelium is already specified into discrete domains with distinctive gene expression profiles at embryonic day 14, with Gsc as a marker gene of the MC lineage. Ptch1 deficiency leads to defective specification of MC precursors along the cochlear basal-apical regions. We demonstrated that elevated Gli2 levels impede MC differentiation through sustaining Otx2 expression and maintaining the progenitor state of MC precursors. Our results uncover an early specification of cochlear non-sensory epithelial cells and establish a crucial role of the Ptch1-Gli2 axis in regulating the development of SV.

Competing Interests: Declaration of interests The authors declare no competing interests.

Titel:	Ptch1 is essential for cochlear marginal cell differentiation and stria vascularis formation.
Autor/in / Beteiligte Person:	Qin, T ; So, KKH ; Hui, CC ; Sham, MH
Link:	Full Text Finder (Volltext)
Zeitschrift:	Cell reports, Jg. 43 (2024-04-23), Heft 4, S. 114083
Veröffentlichung:	[Cambridge, MA] : Cell Press, c 2012-, 2024
Medientyp:	academicJournal
ISSN:	2211-1247 (electronic)
DOI:	10.1016/j.celrep.2024.114083
Schlagwort:	Animals Mice Signal Transduction Zinc Finger Protein Gli2 metabolism Zinc Finger Protein Gli2 genetics Hedgehog Proteins metabolism Hedgehog Proteins genetics Patched-1 Receptor metabolism Patched-1 Receptor genetics Cell Differentiation Stria Vascularis metabolism Stria Vascularis cytology Cochlea metabolism Cochlea embryology Cochlea cytology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural Language: English [Cell Rep] 2024 Apr 23; Vol. 43 (4), pp. 114083. <i>Date of Electronic Publication: </i>2024 Apr 10. MeSH Terms: Patched-1 Receptor* / metabolism ; Patched-1 Receptor* / genetics ; Cell Differentiation* ; Stria Vascularis* / metabolism ; Stria Vascularis* / cytology ; Cochlea* / metabolism ; Cochlea* / embryology ; Cochlea* / cytology ; Animals ; Mice ; Signal Transduction ; Zinc Finger Protein Gli2 / metabolism ; Zinc Finger Protein Gli2 / genetics ; Hedgehog Proteins / metabolism ; Hedgehog Proteins / genetics Contributed Indexing: Keywords: CP: Developmental biology; Gli2; Ptch1; Shh signaling pathway; cochlea; marginal cell; stria vascularis Substance Nomenclature: 0 (Patched-1 Receptor) ; 0 (Ptch1 protein, mouse) ; 0 (Zinc Finger Protein Gli2) ; 0 (Hedgehog Proteins) Entry Date(s): Date Created: 20240411 Date Completed: 20240426 Latest Revision: 20240430 Update Code: 20240430

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