Expression patterns of Irx genes in the developing chick inner ear

Abstract

The vertebrate inner ear is a complex three-dimensional sensorial structure with auditory and vestibular functions. The molecular patterning of the developing otic epithelium creates various positional identities, consequently leading to the stereotyped specification of each neurosensory and non-sensory element of the membranous labyrinth. The Iroquois (Iro/Irx) genes, clustered in two groups (A: Irx1, Irx2, and Irx4; and B: Irx3, Irx5, and Irx6), encode for transcriptional factors involved directly in numerous patterning processes of embryonic tissues in many phyla. This work presents a detailed study of the expression patterns of these six Irx genes during chick inner ear development, paying particular attention to the axial specification of the otic anlagen. The Irx genes seem to play different roles at different embryonic periods. At the otic vesicle stage (HH18), all the genes of each cluster are expressed identically. Both clusters A and B seem involved in the specification of the lateral and posterior portions of the otic anlagen. Cluster B seems to regulate a larger area than cluster A, including the presumptive territory of the endolymphatic apparatus. Both clusters seem also to be involved in neurogenic events. At stages HH24/25-HH27, combinations of IrxA and IrxB genes participate in the specification of most sensory patches and some non-sensory components of the otic epithelium. At stage HH34, the six Irx genes show divergent patterns of expression, leading to the final specification of the membranous labyrinth, as well as to cell differentiation.

Characterization of Wnt and Notch-Responsive Lgr5+ Hair Cell Progenitors in the Striolar Region of the Neonatal Mouse Utricle

“…Sox21 is normally expressed by sensory progenitors within the vestibular and auditory regions (Freeman and Daudet, 2012 ). The Iroquois ( Iro / Irx ) genes encode a family of homeodomain-containing TFs that possibly contribute to the neurogenic processes involved in forming the acoustic and vestibular ganglia (Cardeña-Núñez et al, 2017 ).…”

Cyp1B1 expression patterns in the developing chick inner ear

“…In the developing neural tube, Irx3 is induced by RA and repressed by FGF, and in embryos deficient in RA signaling, expression of Irx3 is severely reduced . In the chick otic vesicle, Irx genes are absent or weakly expressed in the presumptive territory of the Raldh3 ‐positive endolymphatic apparatus, suggesting a repression of Irx genes during the development of this nonsensory element . However, RA inhibits Irx1 and Irx2 expressions through a BMP‐independent mechanism in the developing chick limb .…”

“…129 In the chick otic vesicle, Irx genes are absent or weakly expressed in the presumptive territory of the Raldh3-positive endolymphatic apparatus, 109,130 suggesting a repression of Irx genes during the development of this nonsensory element. 130 However, RA inhibits Irx1 and Irx2 expressions through a BMP-independent mechanism in the developing chick limb. 131 The possible implication of RA in inducing or repressing Irx gene expressions needs further consideration in the developing vertebrate inner ear.…”

Iroquois Homeodomain transcription factors in ventricular conduction system and arrhythmia

“…Irx gene family consists of Irx1 , Irx2 and Irx4 in the IrxA cluster, and Irx3 , Irx5 and Irx6 in the IrxB cluster in mouse and human 20 (Figure 1 ), 11 genes, Ziro1a, 2a, 4a of IrxAa, Ziro1b, 4b of IrxAb, Ziro3a, 5a, 6a of IrxBa, Ziro3b, 5b of IrxBb and Ziro7 in Zebrafish 21 - 24 . In vertebrates, Irx gene family members encode highly conserved homeodomain-containing transcription factors of a 13 amino-acid domain (the Iro box) and the 3-amino-acid-loop-extension (TALE) family 25 (Figure 2 ), which are required for the opportune patterning and formation of the nervous system 26 - 31 and the heart 32 , specification of the membranous labyrinth 33 and nephron segment fate during kidney development 34 - 36 , lung development and maturation 37 , pancreatic, retinal and microvascular endothelial cell development and function 38 - 40 , female gonad 41 and early limb development 42 and also give an advantage to morbid obesity, type 2 diabetes mellitus 43 , fused toes 44 and tumor cells 45 . In the heart, all the Irx transcription factors are expressed in unique and overlapping patterns, abnormality or absence of encoding Irx may cause congenital structural heart disease 46 , cardiomyopathy 47 , 48 and a variety of arrhythmia 49 .…”