Sequential requirement of Sox4 and Sox11 during development of the sympathetic nervous system

Abstract

SUMMARYThe highly related transcription factors Sox4 and Sox11 are expressed in the developing sympathetic nervous system. In the mouse, Sox11 appears first, whereas Sox4 is prevalent later. Using mouse mutagenesis and overexpression strategies in chicken, we studied the role of both SoxC proteins in this tissue. Neither Sox4 nor Sox11 predominantly functioned by promoting pan-neuronal or noradrenergic differentiation of sympathetic neurons as might have been expected from studies in neuronal precursors of the central nervous system. The transcriptional network that regulates the differentiation of sympathetic neurons remained intact and expression of noradrenergic markers showed only minor alterations. Instead, Sox11 was required in early sympathetic ganglia for proliferation of tyrosine hydroxylase-expressing cells, whereas Sox4 ensured the survival of these cells at later stages. In the absence of both Sox4 and Sox11, sympathetic ganglia remained hypoplastic throughout embryogenesis because of consecutive proliferation and survival defects. As a consequence, sympathetic ganglia were rudimentary in the adult and sympathetic innervation of target tissues was impaired leading to severe dysautonomia.

Transcription Factors SOX4 and SOX11 Function Redundantly to Regulate the Development of Mouse Retinal Ganglion Cells

“…Ablation of both factors greatly reduced the survival of neural and mesenchymal progenitor cells during organogenesis (17), as well as of neuron progenitor cells during the spinal cord development (22). While Sox11 was reported to play an indispensable role in the proliferation of tyrosine hydroxylase expressing cells at early stages, Sox4 is crucial to their survival at late stages (21). Further lines of evidence demonstrate that Sox11 also helps improve the survival of differentiated post-mitotic sensory neurons (19).…”

Syntenin-mediated regulation of Sox4 proteasomal degradation modulates transcriptional output

“…It has been described that SoxC family members have overlapping expression patterns and molecular properties (Dy et al, 2008). Sox4 and Sox11 have both been implicated in cardiac and neuronal development, whereas Sox12 appears redundant (Bergsland et al, 2006;Hoser et al, 2008;Bhattaram et al, 2010;Potzner et al, 2010). As C-terminal domains of other Sox family members diverge from SoxC family members, protea-somal regulation of Sox proteins appears confined to the SoxC family.…”

Sox11 regulates survival and axonal growth of embryonic sensory neurons

“…SoxC proteins are also important for development of the sympathetic nervous system (Potzner et al, 2010). In the sympathetic ganglia, Sox11 is predominantly expressed in actively dividing neural progenitors and not so much in postmitotic cells; while in DRG and TG, Sox11 is predominantly expressed in postmitotic neurons but not in dividing cells.…”

“…In the CNS, overexpression of Sox11 promotes neuronal maturation in the developing chick neural tube (Bergsland et al, 2006). In the PNS, a recent report showed that Sox4 and Sox11 are required for sympathetic neuron development (Potzner et al, 2010). We are particularly interested in Sox11, whose expression is the most robust in the nervous system.…”