A Sox10 enhancer element common to the otic placode and neural crest is activated by tissue-specific paralogs

Abstract

SUMMARYThe otic placode, a specialized region of ectoderm, gives rise to components of the inner ear and shares many characteristics with the neural crest, including expression of the key transcription factor Sox10. Here, we show that in avian embryos, a highly conserved cranial neural crest enhancer, Sox10E2, also controls the onset of Sox10 expression in the otic placode. Interestingly, we show that different combinations of paralogous transcription factors (Sox8, Pea3 and cMyb versus Sox9, Ets1 and cMyb) are required to mediate Sox10E2 activity in the ear and neural crest, respectively. Mutating their binding motifs within Sox10E2 greatly reduces enhancer activity in the ear. Moreover, simultaneous knockdown of Sox8, Pea3 and cMyb eliminates not only the enhancer-driven reporter expression, but also the onset of endogenous Sox10 expression in the ear. Rescue experiments confirm that the specific combination of Myb together with Sox8 and Pea3 is responsible for the onset of Sox10 expression in the otic placode, as opposed to Myb plus Sox9 and Ets1 for neural crest Sox10 expression. Whereas SUMOylation of Sox8 is not required for the initial onset of Sox10 expression, it is necessary for later otic vesicle formation. This new role of Sox8, Pea3 and cMyb in controlling Sox10 expression via a common otic/neural crest enhancer suggests an evolutionarily conserved function for the combination of paralogous transcription factors in these tissues of distinct embryological origin. KEY WORDS: Ear, Cis-regulation, Sox10, ChickA Sox10 enhancer element common to the otic placode and neural crest is activated by tissue-specific paralogs

Hypoxia promotes production of neural crest cells in the embryonic head

“…SOX10 is also expressed in otic vesicles (Betancur et al, 2011), which can serve as a staining control. Similar to SNAIL2, ex ovo cultured embryos showed downregulation of SOX10 in neural crest cells, although the expression in the otic vesicle was not affected (Fig.…”

A genome-wide assessment of the ancestral neural crest gene regulatory network

“…Gain-of-function cis-regulatory changes, such as the appearance of new transcription factor binding sites, likely facilitated co-option of preexisting gene batteries, including the pro-chondrocytic SoxE genes and other mesenchymal gene programs, into neural crest-like cells at the neural plate border 2 . Indeed, we show that the lamprey SoxE1 enhancer harbours conserved binding site motifs for several important neural crest transcription factors, including Tfap and SoxE factors, which are known to activate and maintain SoxE transcription in the chick 56,57 , zebrafish 58 and lamprey 29 . HoxA2/B3 sites are also present and possibly control the activity pattern of the enhancer confined to specific regions of cranial neural crest conserved across vertebrate taxa 43 .…”

Genomic Strategies for Terminal Cell Fate Specification

“…It is interesting that the same sox10 CRM functions in the otic placode where it utilizes a different set of paralogous regulators, viz. Sox8 instead of Sox9, and Pea3 instead of Ets1 (Betancur et al, 2011). An aspect additionally illuminated by this sox10 enhancer is that it operates only in the cranial neural crest, while a different enhancer mediates sox10 expression in the vagal neural crest, implying diversity in the neural crest regulatory states along the axis.…”