Einzeltreffer — DigiBib

During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenous SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.

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

Titel:	Cytoneme signaling provides essential contributions to mammalian tissue patterning.
Autor/in / Beteiligte Person:	Hall, ET ; Dillard, ME ; Cleverdon, ER ; Zhang, Y ; Daly, CA ; Ansari, SS ; Wakefield, R ; Stewart, DP ; Pruett-Miller, SM ; Lavado, A ; Carisey, AF ; Johnson, A ; Wang, YD ; Selner, E ; Tanes, M ; Ryu, YS ; Robinson, CG ; Steinberg, J ; Ogden, SK
Zeitschrift:	Cell, Jg. 187 (2024-01-18), Heft 2, S. 276-293.e23
Veröffentlichung:	Cambridge, Ma : Cell Press ; <i>Original Publication</i>: Cambridge, MIT Press., 2024
Medientyp:	academicJournal
ISSN:	1097-4172 (electronic)
DOI:	10.1016/j.cell.2023.12.003
Schlagwort:	Animals Mice Biological Transport Hedgehog Proteins metabolism Pseudopodia metabolism Cell Membrane Structures metabolism Myosins metabolism Signal Transduction Neural Tube cytology Neural Tube metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Cell] 2024 Jan 18; Vol. 187 (2), pp. 276-293.e23. <i>Date of Electronic Publication: </i>2024 Jan 02. MeSH Terms: Cell Membrane Structures* / metabolism ; Myosins* / metabolism ; Signal Transduction* ; Neural Tube* / cytology ; Neural Tube* / metabolism ; Animals ; Mice ; Biological Transport ; Hedgehog Proteins / metabolism ; Pseudopodia / metabolism References: Elife. 2021 Oct 26;10:. (PMID: 34698632) ; Science. 2019 Mar 1;363(6430):948-955. (PMID: 30819957) ; Science. 2011 Apr 15;332(6027):354-8. (PMID: 21493861) ; Cell Rep. 2012 Aug 30;2(2):308-20. (PMID: 22902404) ; Sci Rep. 2019 Mar 12;9(1):4194. (PMID: 30862905) ; Development. 2001 Apr;128(8):1253-64. (PMID: 11262227) ; Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6548-53. (PMID: 16611729) ; Cell. 1999 May 28;97(5):599-607. 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(PMID: 30340023) Grant Information: F31 HD110256 United States HD NICHD NIH HHS; P30 CA021765 United States CA NCI NIH HHS; R35 GM122546 United States GM NIGMS NIH HHS Contributed Indexing: Keywords: Myosin 10; cell signaling; cytoneme; disptached; morphogen; neural tube; signal transduction; sonic hedgehog; tissue patterning Substance Nomenclature: 0 (Hedgehog Proteins) ; 0 (Myo10 protein, mouse) ; EC 3.6.4.1 (Myosins) Entry Date(s): Date Created: 20240103 Date Completed: 20240129 Latest Revision: 20240206 Update Code: 20240206 PubMed Central ID: PMC10842732

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Cytoneme signaling provides essential contributions to mammalian tissue patterning.