PMID- 34547456
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20221202
IS  - 1872-7298 (Electronic)
IS  - 1567-133X (Print)
IS  - 1567-133X (Linking)
VI  - 42
DP  - 2021 Dec
TI  - Spatial and temporal expression of PORCN is highly dynamic in the developing 
      mouse cochlea.
PG  - 119214
LID - S1567-133X(21)00049-1 [pii]
LID - 10.1016/j.gep.2021.119214 [doi]
AB  - The mammalian organ of Corti is a highly specialized sensory organ of the cochlea 
      with a fine-grained pattern that is essential for auditory function. The sensory 
      epithelium, the organ of Corti consists of a single row of inner hair cells and 
      three rows of outer hair cells that are intercalated by support cells in a mosaic 
      pattern. Previous studies show that the Wnt pathway regulates proliferation, 
      promotes medial compartment formation in the cochlea, differentiation of the 
      mechanosensory hair cells and axon guidance of Type II afferent neurons. WNT 
      ligand expressions are highly dynamic throughout development but are insufficient 
      to explain the roles of the Wnt pathway. We address a potential way for how WNTs 
      specify the medial compartment by characterizing the expression of Porcupine 
      (PORCN), an O-acyltransferase that is required for WNT secretion. We show PORCN 
      expression across embryonic ages (E)12.5 - E14.5, E16.5, and postnatal day (P)1. 
      Our results showed enriched PORCN in the medial domains during early stages of 
      development, indicating that WNTs have a stronger influence on patterning of the 
      medial compartment. PORCN was rapidly downregulated after E14.5, following the 
      onset of sensory cell differentiation; residual expression remained in some hair 
      cells and supporting cells. On E14.5 and E16.5, we also examined the spatial 
      expression of Gsk3beta, an inhibitor of canonical Wnt signaling to determine its 
      potential role in radial patterning of the cochlea. Gsk3beta was broadly expressed 
      across the radial axis of the epithelium; therefore, unlikely to control 
      WNT-mediated medial specification. In conclusion, the spatial expression of PORCN 
      enriches WNT secretion from the medial domains of the cochlea to influence the 
      specification of cell fates in the medial sensory domain.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Oliver, Brianna L
AU  - Oliver BL
AD  - The Jackson Laboratory, Bar Harbor, ME, 04609, United States.
FAU - Young, Caryl A
AU  - Young CA
AD  - The Jackson Laboratory, Bar Harbor, ME, 04609, United States; The University of 
      Maine, Graduate School of Biomedical Sciences and Engineering, Orono, ME, 04469, 
      United States.
FAU - Munnamalai, Vidhya
AU  - Munnamalai V
AD  - The Jackson Laboratory, Bar Harbor, ME, 04609, United States; The University of 
      Maine, Graduate School of Biomedical Sciences and Engineering, Orono, ME, 04469, 
      United States. Electronic address: vidhya.munnamalai@jax.org.
LA  - eng
GR  - R21 DC016376/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210920
PL  - Netherlands
TA  - Gene Expr Patterns
JT  - Gene expression patterns : GEP
JID - 101167473
RN  - 0 (Membrane Proteins)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (Porcn protein, mouse)
SB  - IM
MH  - Acyltransferases/metabolism
MH  - Animals
MH  - Cell Differentiation
MH  - Cochlea/metabolism
MH  - Hair Cells, Auditory/metabolism
MH  - Membrane Proteins
MH  - Mice
MH  - *Porcupines/metabolism
MH  - Wnt Signaling Pathway
PMC - PMC8665061
MID - NIHMS1742968
OTO - NOTNLM
OT  - Cochlea
OT  - GSK3beta
OT  - Porcupine
OT  - Wnt
OT  - Wntless
COIS- Declarations of Interest: The authors declare no conflict of interest.
EDAT- 2021/09/22 06:00
MHDA- 2022/01/14 06:00
PMCR- 2022/12/01
CRDT- 2021/09/21 20:17
PHST- 2021/08/04 00:00 [received]
PHST- 2021/09/08 00:00 [revised]
PHST- 2021/09/17 00:00 [accepted]
PHST- 2021/09/22 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2021/09/21 20:17 [entrez]
PHST- 2022/12/01 00:00 [pmc-release]
AID - S1567-133X(21)00049-1 [pii]
AID - 10.1016/j.gep.2021.119214 [doi]
PST - ppublish
SO  - Gene Expr Patterns. 2021 Dec;42:119214. doi: 10.1016/j.gep.2021.119214. Epub 2021 
      Sep 20.