Competing signals drive telencephalon diversity

Abstract

The telencephalon is the most complex brain region, controlling communication, emotion, movement and memory. Its adult derivatives develop from the dorsal pallium and ventral subpallium. Despite knowledge of genes required in these territories, we do not understand how evolution has shaped telencephalon diversity. Here, using rock-and sand-dwelling cichlid fishes from Lake Malawi, we demonstrate that differences in strength and timing of opposing Hedgehog and Wingless signals establish evolutionary divergence in dorsal-ventral telencephalon patterning. Rock dwellers exhibit early, extensive Hedgehog activity in the ventral forebrain resulting in expression of foxg1 before dorsal Wingless signals, and a larger subpallium. Sand dwellers show rapid deployment of Wingless, later foxg1 expression and a larger pallium. Manipulation of the Hedgehog and Wingless pathways in cichlid and zebrafish embryos is sufficient to mimic differences between rock-versus sand-dweller brains. Our data suggest that competing ventral Hedgehog and dorsal Wingless signals mediate evolutionary diversification of the telencephalon.

Wnt signalling underlies the evolution of new phenotypes and craniofacial variability in Lake Malawi cichlids

“…In order to test this prediction, we treated stage 17 LF larvae with the Wnt antagonist 13 IWR-1 (Enzo Life Sciences) for 12 h. Control animals were incubated in DMSO. Larvae were treated with 10–12 μM of IWR-1, based on previously published data in cichlids 31,32 . Following treatment larvae were washed in system water three times, and placed back into a clean beaker to be reared to stage 21 (8 dpf), when they were cleared and stained as above.…”

Six3 dosage mediates the pathogenesis of holoprosencephaly

“…n=3 control; n=5 Six3 neo/− . catenin signaling pathways during dorsoventral patterning of the telencephalon (Danesin et al, 2009;Sylvester et al, 2013). Briefly, Shh activates foxg1 expression in the ventral forebrain and, in turn, Foxg1 is cell-autonomously required for the specification of the ventral telencephalon; Foxg1 also restricts the dorsal telencephalon by repressing wnt8b expression (Danesin et al, 2009).…”

Cichlid fishes as a model to understand normal and clinical craniofacial variation

“…The choice of whether to examine the mechanism of gene action within cichlids themselves or within traditional model organisms is dependent on the particulars of the candidate gene or pathway. Cichlids are readily susceptible to pharmacological manipulations through addition of small molecules to their water (Bloomquist, et al 2015; Fraser, et al 2008; Fraser, et al 2013; Hu and Albertson 2014; Parsons and Albertson 2013; Parsons, et al 2014; Powder, et al 2015; Roberts, et al 2011; Sylvester, et al 2010; Sylvester, et al 2013). These chemicals have varying degrees of target specificity (i.e.…”