Ankmy2 Prevents Smoothened-Independent Hyperactivation of the Hedgehog Pathway via Cilia-Regulated Adenylyl Cyclase Signaling.
The mechanisms underlying subcellular targeting of cAMP-generating adenylyl cyclases and processes regulated by their compartmentalization are poorly understood. Here, we identify Ankmy2 as a repressor of the Hedgehog pathway via adenylyl cyclase targeting. Ankmy2 binds to multiple adenylyl cyclases, determining their maturation and trafficking to primary cilia. Mice lacking Ankmy2 are mid-embryonic lethal. Knockout embryos have increased Hedgehog signaling and completely open neural tubes showing co-expansion of all ventral neuroprogenitor markers, comparable to the loss of the Hedgehog receptor Patched1. Ventralization in Ankmy2 knockout is completely independent of the Hedgehog pathway transducer Smoothened. Instead, ventralization results from the reduced formation of Gli2 and Gli3 repressors and early depletion of adenylyl cyclase III in neuroepithelial cilia, implicating deficient pathway repression. Ventralization in Ankmy2 knockout requires both cilia and Gli2 activation. These findings indicate that cilia-dependent adenylyl cyclase signaling represses the Hedgehog pathway and promotes morphogenetic patterning.
Pubmed ID: 32702291 RIS Download
Additional research tools detected in this publication
Antibodies used in this publication
- Goat Anti-DDDDK tag Polyclonal Antibody, Unconjugated (RRID:AB_299216)
- TIMM50 antibody (RRID:AB_778461)
- PGK1 antibody (RRID:AB_2037666)
- GLI1 (L42B10) Mouse mAb (RRID:AB_2294746)
- Goat Anti-Mouse Gli-2 Affinity purified Polyclonal antibody, Unconjugated (RRID:AB_2111902)
- Goat Anti-GLI-3, aa 1-479 Affinity purified Polyclonal antibody, Unconjugated (RRID:AB_2232499)
- Anti-HA High Affinity; Rat monoclonal antibody (clone 3F10) (RRID:AB_390918)
- Monoclonal Anti-alpha-Tubulin antibody produced in mouse (RRID:AB_477583)
- Anti-ANKMY2 polyclonal antibody (RRID:AB_2685777)
- GFP-avictoria (RRID:AB_303395)
- Anti-GFP antibody (RRID:AB_300798)
- Mouse Anti-Tubulin, gamma Monoclonal Antibody, Unconjugated, Clone GTU-88 (RRID:AB_297920)
- A cyclase III (C-20) (RRID:AB_630839)
- Pax7 antibody - Kawakami, A.; Tokyo Institute of Technology (RRID:AB_528428)
- Purified anti-Pax-6 (RRID:AB_2749901)
- Anti-Olig2 Antibody, clone 211F1.1 (RRID:AB_10807410)
- Nkx2.2 transcription factor antibody - Jessell, T.M. / Brenner-Morton, S.; HHMI/Columbia University (RRID:AB_531794)
- Homeobox protein Nkx-6.1; Nkx6.1 antibody - Madsen, O.D.; Hagedorn Research Institute (RRID:AB_532378)
- FOXA2 antibody [EPR4466] (RRID:AB_11157157)
- FOXA2 antibody (RRID:AB_732411)
- Arl13b (RRID:AB_2750771)
- Monoclonal Anti-Tubulin, Acetylated antibody produced in mouse (RRID:AB_477585)
Associated grants
- Agency: NIGMS NIH HHS, United States
Id: R01 GM113023 - Agency: NCRR NIH HHS, United States
Id: S10 RR029731
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NIH 3T3 (tool)
RRID:CVCL_0594
Cell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentions3T3-L1 (tool)
RRID:CVCL_0123
Cell line 3T3-L1 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsGoat Anti-DDDDK tag Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_299216
This polyclonal targets DDDDK tag
View all literature mentionsTIMM50 antibody (antibody)
RRID:AB_778461
This polyclonal targets Human TIMM50
View all literature mentionsGLI1 (L42B10) Mouse mAb (antibody)
RRID:AB_2294746
This monoclonal targets GLI1
View all literature mentionsGoat Anti-Mouse Gli-2 Affinity purified Polyclonal antibody, Unconjugated (antibody)
RRID:AB_2111902
This polyclonal targets Mouse GLI-2
View all literature mentionsGoat Anti-GLI-3, aa 1-479 Affinity purified Polyclonal antibody, Unconjugated (antibody)
RRID:AB_2232499
This polyclonal targets GLI-3
View all literature mentionsAnti-HA High Affinity; Rat monoclonal antibody (clone 3F10) (antibody)
RRID:AB_390918
This monoclonal targets HA
View all literature mentionsMonoclonal Anti-alpha-Tubulin antibody produced in mouse (antibody)
RRID:AB_477583
This monoclonal targets alpha-Tubulin
View all literature mentionsAnti-ANKMY2 polyclonal antibody (antibody)
RRID:AB_2685777
This polyclonal targets ANKMY2
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RRID:AB_300798
This polyclonal targets GFP
View all literature mentionsMouse Anti-Tubulin, gamma Monoclonal Antibody, Unconjugated, Clone GTU-88 (antibody)
RRID:AB_297920
This monoclonal targets gamma Tubulin
View all literature mentionsA cyclase III (C-20) (antibody)
RRID:AB_630839
This polyclonal targets ADCY3
View all literature mentionsPax7 antibody - Kawakami, A.; Tokyo Institute of Technology (antibody)
RRID:AB_528428
This monoclonal targets Pax7
View all literature mentionsPurified anti-Pax-6 (antibody)
RRID:AB_2749901
This unknown targets Pax-6
View all literature mentionsAnti-Olig2 Antibody, clone 211F1.1 (antibody)
RRID:AB_10807410
This monoclonal targets Olig2
View all literature mentionsNkx2.2 transcription factor antibody - Jessell, T.M. / Brenner-Morton, S.; HHMI/Columbia University (antibody)
RRID:AB_531794
This monoclonal targets Nkx2.2 transcription factor
View all literature mentionsHomeobox protein Nkx-6.1; Nkx6.1 antibody - Madsen, O.D.; Hagedorn Research Institute (antibody)
RRID:AB_532378
This monoclonal targets Homeobox protein Nkx-6.1; Nkx6.1
View all literature mentionsFOXA2 antibody [EPR4466] (antibody)
RRID:AB_11157157
This monoclonal targets FOXA2 antibody [EPR4466]
View all literature mentionsFOXA2 antibody (antibody)
RRID:AB_732411
This polyclonal targets FOXA2 antibody
View all literature mentionsMonoclonal Anti-Tubulin, Acetylated antibody produced in mouse (antibody)
RRID:AB_477585
This monoclonal targets Tubulin Acetylated
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RRID:CVCL_0429
Cell line mIMCD-3 is a Transformed cell line with a species of origin Mus musculus
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RRID:CVCL_0190
Cell line C3H/10T1/2 clone 8 is a Spontaneously immortalized cell line with a species of origin Mus musculus
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RRID:IMSR_JAX:003081
Mus musculus with name STOCK Ptch1tm1Mps/J from IMSR.
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RRID:IMSR_JAX:022409
Mus musculus with name B6.129P2-Ift88tm1Bky/J from IMSR.
View all literature mentions
