Msxb is a core component of the genetic circuitry specifying the dorsal and ventral neurogenic midlines in the ascidian embryo

Abstract

The tail ascidian larval peripheral nervous system is made up of epidermal sensory neurons distributed more or less regularly in ventral and dorsal midlines. Their formation occurs in two-steps: the ventral and dorsal midlines are induced as neurogenic territories by Fgf9/16/20 and Admp respectively. The Delta2/Notch interaction then controls the number of neurons that form. The genetic machinery acting between the inductive processes taking place before gastrulation and neuron specification at tailbud stages are largely unknown. The analysis of seven transcription factors expressed in the forming midlines revealed an unexpected complexity and dynamic of gene expression. Their systematic overexpression confirmed that these genes do not interact following a linear cascade of activation. However, the integration of our data revealed the distinct key roles of the two upstream factors Msxb and Nkx-C that are the earliest expressed genes and the only ones able to induce neurogenic midline and ESN formation. Our data suggest that Msxb would be the primary midline gene integrating inputs from the ventral and dorsal inducers and launching a pan-midline transcriptional program. Nkx-C would be involved in tail tip specification, in maintenance of the pan-midline network and in a posterior to anterior wave controlling differentiation.

Conservation of peripheral nervous system formation mechanisms in divergent ascidian embryos

“…Fgf9/16/20 as the inducer of the dorsal neurogenic midline (DML) and Admp as the inducer of the ventral neurogenic midline (VML). While function and regulatory interactions have been determined for several genes, direct interactions and associated CRMs are unknown for the most part (Fig 1-supplement 1A) (14,42,44,46,48,52). Here, we have focused our work on seven TFs that are expressed in both ventral and dorsal caudal neurogenic midlines (VDML) and for which we have already described regulatory interactions that generated a provisional GRN (42,44).…”

“…We have studied a subset of the GRN controlling caudal peripheral nervous system (PNS) formation. Caudal PNS formation is well understood in Ciona intestinalis both at the level of the developmental and cellular processes, and at the level of the molecular regulators (14,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). First, dorsal and ventral epidermis midlines are induced as neurogenic territories respectively by Fgf and Bmp signals from the underlying endomesodermal cells.…”

Lateral neural borders as precursors of peripheral nervous systems: A comparative view across bilaterians

“…So, like vertebrate NPB, the Ciona counterpart give rise to both migratory and non‐migratory PNS neurons. Furthermore, Ciona NPB also expresses orthologs of vertebrate “neural‐plate‐border module,” including Msx , Zic and Pax3 / 7 and juxtapose with Dlx ‐expressing non‐neurogenic ectoderm, and Msx also plays a critical role in the specification of NPB in Ciona , as it is in vertebrates (Li et al., ; Roure & Darras, ; Stolfi et al., ; Waki et al., ). At last, Ciona NPB cell lineage expresses some critical features of vertebrate NBP derivatives: neural crest and placode.…”

The central nervous system of ascidian larvae

“…In contrast, the ventral CENs arise far from the neural plate (Figure (a), lower panel). The mechanisms of CEN specification are well elucidated but will not be discussed here …”