Gene regulatory networks underlying the compartmentalization of theCionacentral nervous system

Abstract

The tripartite organization of the central nervous system (CNS) may be an ancient character of the bilaterians. However, the elaboration of the more complex vertebrate brain depends on the midbrain-hindbrain boundary (MHB)organizer, which is absent in invertebrates such as Drosophila. The Fgf8 signaling molecule expressed in the MHB organizer plays a key role in delineating separate mesencephalon and metencephalon compartments in the vertebrate CNS. Here, we present evidence that an Fgf8 ortholog establishes sequential patterns of regulatory gene expression in the developing posterior sensory vesicle, and the interleaved `neck' region located between the sensory vesicle and visceral ganglion of the simple chordate Ciona intestinalis. The detailed characterization of gene networks in the developing CNS led to new insights into the mechanisms by which Fgf8/17/18 patterns the chordate brain. The precise positioning of this Fgf signaling activity depends on an unusual AND/OR network motif that regulates Snail, which encodes a threshold repressor of Fgf8expression. Nodal is sufficient to activate low levels of the Snail repressor within the neural plate, while the combination of Nodal and Neurogenin produces high levels of Snailin neighboring domains of the CNS. The loss of Fgf8 patterning activity results in the transformation of hindbrain structures into an expanded mesencephalon in both ascidians and vertebrates, suggesting that the primitive MHB-like activity predates the vertebrate CNS.

A direct role for murine Cdx proteins in the trunk neural crest-gene regulatory network

“…One set is derived from the 'a' lineage and contributes to structures equivalent to the vertebrate eye and inner ear (Abitua et al, 2012;Nishida and Satoh, 1989), whereas the other is derived from the 'A' lineage and contributes to body pigmentation (Jeffery et al, 2008(Jeffery et al, , 2004. We believe that the controversy concerning which set of pigment cells is the 'true' NC precursor could be resolved in accordance with the fact that the ascidian central nervous system is compartmentalized in a similar way to that of vertebrates (Imai et al, 2009), i.e. the origin of the cranial NC could be attributed to the a-derived set, whereas the origin of the trunk NC could be attributed to the Aderived set.…”

Nodal and FGF coordinate ascidian neural tube morphogenesis

“…Nuclei were labeled by electroporation of a FoxB>H2B:YFP reporter gene (Imai et al, 2009), which recapitulates endogenous FoxB expression in A7.4, A7.6 and A7.8, and later in the lateral epidermis during neurulation (Imai et al, 2004;Fig. S1).…”

“…FoxB, Snail, and ETR regulatory sequences have been reported previously (Corbo et al, 1997;Imai et al, 2009;Veeman et al, 2010). The Mnx −5 kb regulatory sequence was amplified from genomic DNA using the primers F-TATGGCGCGCCTCCTGATGTGACGGATTTATGACTG, R-TATG-CGGCCGCTAGCATCATTTTAAATCTTAAATATCAAAGGTTC and cloned into a H2B:Cherry-containing expression vector using NotI and AscI restriction sites.…”

FGF signaling establishes the anterior border of the Ciona neural tube

“…In Ciona, neural induction begins with Otx expression at the 32-cell stage in the anterior neurectoderm via GATA and Ets transcription factors in response to FGF signaling (Bertrand et al, 2003). The requirement for FGF signaling persists in later development, when it is required for patterning posterior components of the nervous system Imai et al, 2009;. Thus, FGF signaling acts at both early and late stages of Ciona nervous system development.…”