Abstract
The mammalian hearing organ is a stereotyped cellular assembly with orderly innervation: two types of spiral ganglion neurons (SGNs) innervate two types of differentially distributed hair cells (HCs). HCs and SGNs evolved from single neurosensory cells through gene multiplication and diversification. Independent regulation of HCs and neuronal differentiation through expression of basic Helix-loop-Helix transcription factors (bHLH TFs: Atoh1, Neurog1, Neurod1) led to the evolution of vestibular HC assembly and their unique type of innervation. In ancestral mammals, a vestibular organ was transformed into the organ of Corti (OC) containing a single row of inner HC (IHC), three rows of outer HCs (OHCs), several unique supporting cell types, and a peculiar innervation distribution. Restoring the OC following long-term hearing loss is complicated by the fact that the entire organ is replaced by a flat epithelium and requires reconstructing the organ from uniform undifferentiated cell types, recapitulating both evolution and development. Finding the right sequence of gene activation during development that is useful for regeneration could benefit from an understanding of the OC evolution. Toward this end, we report on Foxg1 and Lmx1a mutants that radically alter the organ of Corti (OC) cell assembly and its innervation when mutated and may have driven the evolutionary reorganization of the basilar papilla into an organ of Corti in ancestral Therapsids. Furthermore, genetically manipulating the level of bHLH TFs changes HC type and distribution and allows inference how transformation of HCs might have happened evolutionarily. We report on how bHLH TFs regulate OHC/IHC and how misexpression (Atoh1-Cre; Atoh1f/kiNeurog1) alters HC fate and supporting cell development. Using mice with altered HC types and distribution, we demonstrate innervation changes driven by HC patterning. Using these insights, we speculate on necessary steps needed to convert a random mixture of postmitotic precursors into the orderly OC through spatially and temporally regulated critical bHLH genes in the context of other TFs to restore normal innervation patterns.Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com
Αναζήτηση αυτού του ιστολογίου
Πληροφορίες
Ετικέτες
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
-
Publication date: Available online 25 July 2018 Source: Journal of Photochemistry and Photobiology B: Biology Author(s): Marco Ballestr...
-
Editorial AJR Reviewers: Heartfelt Thanks From the Editors and Staff Thomas H. Berquist 1 Share + Affiliation: Citation: American Journal...
-
https://www.youtube.com/watch?v=DFOhpBjLqN4&t=1s , Η ΘΕΡΑΠΕΙΑ ΓΙΑ ΟΛΕΣ ΤΙΣ ΑΣΘΕΝΕΙΕΣ 1 Περιεχόμενα Σύντομο βιογραφικό Πρόλογος μεταφραστ...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου
Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.