Comparative expression analysis of POU4F1, POU4F2 and ISL1 in developing mouse cochleovestibular ganglion neurons

Abstract

POU-homeodomain and LIM-homeodomain transcription factors are expressed in developing projection neurons within retina, inner ear, dorsal root ganglion, and trigeminal ganglion, and play synergistic roles in their differentiation and survival. Here, using immunohistochemistry, we present a comparative analysis of the spatiotemporal expression pattern of POU4F1, POU4F2, and ISL1 during the development of cochleovestibular ganglion (CVG) neurons in mouse inner ear. At early stages, when otic neurons are first detected in the otic epithelium (OE) and migrate into periotic mesenchyme to form the CVG, POU4F1 and ISL1 are co-expressed in a majority of the delaminated CVG neurons, which are marked by NEUROD1 expression, but POU4F1 is absent in the otic epithelium. The onset of POU4F2 expression starts after that of POU4F1 and ISL1, and is observed in the NEUROD1-negative, post-mitotic CVG neurons. When the CVG neurons innervate the vestibular and cochlear sensory organs, the expression of POU4F1, POU4F2, and ISL1 continues in both vestibular and spiral ganglion cells. Later in development, POU4F1 expression becomes down-regulated in a majority of spiral ganglion (SG) neurons and more neurons express POU4F2 expression while ISL1 expression is maintained. The differential as well as overlapping expression of POU4F1, POU4F2, and ISL1 combined with previous studies suggests possible functional interaction and regulatory relationship of these transcription factors in the development of inner ear neurons.

Insm1 promotes neurogenic proliferation in delaminated otic progenitors

“…As early as E10.5, we observed Insm1 in the neurogenic DPs at the basal edge of the otocyst and in the mesenchyme. This would indicate that Insm1 is likely expressed after NeuroD, which is downstream of Neurog1 and is expressed in early neuronal progenitors (apical and delaminating) of the otic epithelium (Deng et al, 2014; Kim et al, 2001; Liu et al, 2000; Ma et al, 2000). Several potential functions have been proposed for NeuroD.…”

“…Gata3 has also been conditionally ablated in SpG neurons after neurogenesis and has been shown to be necessary for their axonal pathfinding and survival (Appler et al, 2013; Duncan and Fritzsch, 2013). After DPs delaminate, they express Pou4f1, which contributes to SpG neuron differentiation by regulating cell size and maintaining TrkC expression (Deng et al, 2014; Huang et al, 2001). Following cell cycle exit, differentiating nascent SVG neurons express Pou4f2, whose function has not yet been determined (Deng et al, 2014; Huang et al, 2001).…”

“…After DPs delaminate, they express Pou4f1, which contributes to SpG neuron differentiation by regulating cell size and maintaining TrkC expression (Deng et al, 2014; Huang et al, 2001). Following cell cycle exit, differentiating nascent SVG neurons express Pou4f2, whose function has not yet been determined (Deng et al, 2014; Huang et al, 2001). …”

Expression and function of the LIM-homeodomain transcription factor Islet-1 in the developing and mature vertebrate retina

“…These domains are zinc fingers that coordinate two zinc ions and mediate proteineprotein interactions (Bhati et al, 2008). Studies of diverse vertebrate models have established that the LIM-HD factors are critical for the development of specialized cells in multiple tissue types, including the nervous system (Ericson et al, 1992;Pfaff et al, 1996;Porter et al, 1997;Moreno et al, 2008a,b,c;Deng et al, 2014), the heart (Pandur et al, 2013), the urogenital system (Kobayashi et al, 2004;Kaku et al, 2013), and such endocrine organs such as the pituitary gland (Mullen et al, 2007) and the pancreas (Ahlgren et al, 1997). In the case of the developing vertebrate central nervous system, LIM-HD transcription factors play crucial roles in controlling cell fate specification, survival and differentiation, and axonal projection patterns (Tsuchida et al, 1994;Hobert and Westphal, 2000;Bach, 2000).…”

“…It has been used as a marker of cell types, regional subdivisions, and specific nuclei during development of the central nervous system in different vertebrates (Moreno et al, 2008a,b,c;. It also plays a role in differentiating inner ear neurons in conjunction with other transcription factors (Deng et al, 2014). Finally, Isl1 orchestrates the early differentiation and maintenance of various cell types in the retina of different vertebrates (Table 1).…”