TY - JOUR
T1 - Salvador–Warts–Hippo pathway regulates sensory organ development via caspase-dependent nonapoptotic signaling
AU - Wang, Lan Hsin
AU - Baker, Nicholas E.
N1 - Funding Information:
We thank Hugo Bellen, Claude Desplan, and Masayuki Miura for fly reagents and Sudershana Nair and Venkateswara Reddy for comments on the paper. We appreciate the information provided by the Flybase67. Leica Confocal Imaging was performed in the Analytical Imaging Facility at AECOM supported by the NCI (P30CA013330) and NIH (SIG 1S10OD023591-01). Zeiss confocal microscopy was supported by Neuroscience Core Facility of Academia Sinica (AS-CFII-108-106, Taiwan). L.H.W is funded by the Ministry of Science and Technology of Taiwan (MOST 105-2311-B-016-001-MY2, MOST 107-2311-B-016-001-MY3 and MOST 108-3111-Y-016-008). Research in N.E.B’s laboratory has been supported by grants from the NIH (GM047892 and EY028990).
PY - 2019/9/1
Y1 - 2019/9/1
N2 - The fundamental roles for the Salvador–Warts–Hippo (SWH) pathway are widely characterized in growth regulation and organ size control. However, the function of SWH pathway is less known in cell fate determination. Here we uncover a novel role of the SWH signaling pathway in determination of cell fate during neural precursor (sensory organ precursor, SOP) development. Inactivation of the SWH pathway in SOP of the wing imaginal discs affects caspase-dependent bristle patterning in an apoptosis-independent process. Such nonapoptotic functions of caspases have been implicated in inflammation, proliferation, cellular remodeling, and cell fate determination. Our data indicate an effect on the Wingless (Wg)/Wnt pathway. Previously, caspases were proposed to cleave and activate a negative regulator of Wg/Wnt signaling, Shaggy (Sgg)/GSK3β. Surprisingly, we found that a noncleavable form of Sgg encoded from the endogenous locus after CRISPR-Cas9 modification supported almost normal bristle patterning, indicating that Sgg might not be the main target of the caspase-dependent nonapoptotic process. Collectively, our results outline a new function of SWH signaling that crosstalks to caspase-dependent nonapoptotic signaling and Wg/Wnt signaling in neural precursor development, which might be implicated in neuronal pathogenesis.
AB - The fundamental roles for the Salvador–Warts–Hippo (SWH) pathway are widely characterized in growth regulation and organ size control. However, the function of SWH pathway is less known in cell fate determination. Here we uncover a novel role of the SWH signaling pathway in determination of cell fate during neural precursor (sensory organ precursor, SOP) development. Inactivation of the SWH pathway in SOP of the wing imaginal discs affects caspase-dependent bristle patterning in an apoptosis-independent process. Such nonapoptotic functions of caspases have been implicated in inflammation, proliferation, cellular remodeling, and cell fate determination. Our data indicate an effect on the Wingless (Wg)/Wnt pathway. Previously, caspases were proposed to cleave and activate a negative regulator of Wg/Wnt signaling, Shaggy (Sgg)/GSK3β. Surprisingly, we found that a noncleavable form of Sgg encoded from the endogenous locus after CRISPR-Cas9 modification supported almost normal bristle patterning, indicating that Sgg might not be the main target of the caspase-dependent nonapoptotic process. Collectively, our results outline a new function of SWH signaling that crosstalks to caspase-dependent nonapoptotic signaling and Wg/Wnt signaling in neural precursor development, which might be implicated in neuronal pathogenesis.
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U2 - 10.1038/s41419-019-1924-3
DO - 10.1038/s41419-019-1924-3
M3 - Article
C2 - 31511495
AN - SCOPUS:85072100649
VL - 10
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 9
M1 - 669
ER -