Spemann organizer gene Goosecoid promotes delamination of neuroblasts from the otic vesicle

Abstract

Neurons of the Statoacoustic Ganglion (SAG), which innervate the inner ear, originate as neuroblasts in the floor of the otic vesicle and subsequently delaminate and migrate toward the hindbrain before completing differentiation. In all vertebrates, locally expressed Fgf initiates SAG development by inducing expression of Neurogenin1 (Ngn1) in the floor of the otic vesicle. However, not all Ngn1-positive cells undergo delamination, nor has the mechanism controlling SAG delamination been elucidated. Here we report that Goosecoid (Gsc), best known for regulating cellular dynamics in the Spemann organizer, regulates delamination of neuroblasts in the otic vesicle. In zebrafish, Fgf coregulates expression of Gsc and Ngn1 in partially overlapping domains, with delamination occurring primarily in the zone of overlap. Loss of Gsc severely inhibits delamination, whereas overexpression of Gsc greatly increases delamination. Comisexpression of Ngn1 and Gsc induces ectopic delamination of some cells from the medial wall of the otic vesicle but with a low incidence, suggesting the action of a local inhibitor. The medial marker Pax2a is required to restrict the domain of gsc expression, and misexpression of Pax2a is sufficient to block delamination and fully suppress the effects of Gsc. The opposing activities of Gsc and Pax2a correlate with repression or up-regulation, respectively, of E-cadherin (cdh1). These data resolve a genetic mechanism controlling delamination of otic neuroblasts. The data also elucidate a developmental role for Gsc consistent with a general function in promoting epithelial-to-mesenchymal transition (EMT).

sox2 and sox3 Play unique roles in development of hair cells and neurons in the zebrafish inner ear

“…Transgenic line TG(brn3c:gap43-GFP) (Xiao et al, 2005) was used to visualize sensory hair cells. Transgenic lines TG(hsp70:fgf8a) x17 , TG(hsp70:atoh1a) x20 , TG(hsp70:sox2) x21 (Millimaki et al, 2010), TG(hsp70:sox3) x32 (Gou et al, 2017) and TG(hsp70:ngn1) x28 (Kantarci et al, 2016) used in the misexpression studies here were referred to as hs:fgf8, hs:atoh1a, hs:sox2, hs:sox3 and hs:neurog1 respectively. Embryos were developed under standard conditions at 28.5°C (Kimmel et al, 1995), except during and after heat shock, in fish water containing methylene blue.…”

“…In mammals and birds, neuroblasts arise first and subsequently delaminate from the otic epithelium and are quickly replaced by developing sensory epithelia (Raft and Groves, 2015; Raft et al, 2007). In zebrafish, neuroblasts and sensory epithelia initially form simultaneously in abutting domains in the floor of the otic vesicle, after which neuroblasts delaminate and differentiate in a manner similar to tetrapod vertebrates (Haddon and Lewis, 1996; Kantarci et al, 2016; Millimaki et al, 2007). Despite differences in timing and degree of spatial overlap of neural vs. sensory development, many of the same regulatory genes operate in all vertebrate species.…”

Blast-induced hearing impairment in rats is associated with structural and molecular changes of the inner ear

“…We performed qRT-PCR analysis on Gsc mRNA levels in cochlea, which were DEGs that showed substantial changes following blast exposure. The Gsc protein acts as a transcription factor and is essential for tympanic ring development 28 and inner ear development 29,30 . It is also a crucial regulator of mesodermal patterning in mammals and has specific functions in neural crest cell derivatives 31 .…”

A novel role of the organizer gene Goosecoid as an inhibitor of Wnt/PCP-mediated convergent extension in Xenopus and mouse

“…The analysis of otic vesicle differentiation in zebrafish morphants and TALEN-induced mutants revealed a function for Gsc in the delamination of neuroblasts, i.e. a process involving epithelial-to-mesenchymal transitions associated with cell shape changes and delamination/migration behavior 82 . Inner ear hair cell PCP was not investigated in this study.…”