A gene regulatory network for apical organ neurogenesis and its spatial control in sea star embryos

Abstract

How neural stem cells generate the correct number and type of differentiated neurons in appropriate places remains an important question. Although nervous systems are diverse across phyla, in many taxa the larva forms an anterior concentration of serotonergic neurons, or apical organ. The sea star embryo initially has a panneurogenic ectoderm, but the genetic mechanism that directs a subset of these cells to generate serotonergic neurons in a particular location is unresolved. We show that neurogenesis in sea star larvae begins with soxc-expressing multipotent progenitors. These give rise to restricted progenitors that express lhx2/9. soxc-and lhx2/9-expressing cells can undergo both asymmetric divisions, allowing for progression towards a particular neural fate, and symmetric proliferative divisions. We show that nested concentric domains of gene expression along the anterior-posterior (AP) axis, which are observed in a great diversity of metazoans, control neurogenesis in the sea star larva by promoting particular division modes and progression towards becoming a neuron. This work explains how spatial patterning in the ectoderm controls progression of neurogenesis in addition to providing spatial cues for neuron location. Modification to the sizes of these AP territories provides a simple mechanism to explain the diversity of neuron number among apical organs.

Embryonic neurogenesis in echinoderms

“…It is not known whether this mechanism exists in sea star, but expression of wnt5 , nk1 and pax2/5/8 is expressed similarly in the two taxa (McCauley et al, ; Yankura, Martik, Jennings, & Hinman, ). The remaining more anterior ectoderm is a Wnt negative zone, and therefore when cWnt signaling is experimentally abrogated, the resultant embryos fail to gastrulate, do not develop endoderm or mesoderm, and form permanent blastulae in which the neuroectoderm is expanded and unpatterned (Cheatle Jarvela, Yankura, & Hinman, ; Logan et al, ; Range, Angerer, & Angerer, ; Yaguchi, Yaguchi, & Burke, ).…”

“…In sea stars, the expression of orthologous Wnt and Fzl genes is similarly positioned along the AP axis (McCauley et al, ). Foxq2 is expressed in the anterior most ectoderm, where it is needed to activate the expression of dkk3 , and is necessary for the formation of serotonergic neurons (Cheatle Jarvela et al, ). These data are therefore consistent with sea star APDs being established through interplay between Wnt and Wnt antagonists although the specific interactions observed in sea urchins have not been tested.…”

“…As an example, change in regulation between Six3 and Foxq2 may have minor functional consequence, if other mechanisms maintain foxq2 expression in the APD in sea stars. Conversely some of the differences in the size of the embryonic territories, for example, the large domain of rx expression in sea stars, has been suggested to provide a larger territory for progenitor proliferation (Cheatle Jarvela et al, ). Many of the common features observed among echinoderms are also present in axial organization and neural specification in other animals.…”

“…Some neural progenitors appear to divide giving rise to one cell that persists and a second cell that undergoes apoptosis. In sea star embryos, pairs of cells are interpreted to be the product of a recent cell division and in some instances one of the pair of cells in the animal pole domain can be labeled with EdU (Cheatle Jarvela et al, ). Additionally, in pairs of cells expressing soxC , one of the two cells can also expresses lhx2/9 .…”

cis‐Regulatory analysis for later phase of anterior neuroectoderm‐specific foxQ2 expression in sea urchin embryos

“…The foxQ2 expression in the six3/6 ‐free region has also been reported in protostomes (Kitzmann et al, ; Marlow et al, ; Martín‐Durán et al, ; Santagata et al, ). In addition, a recent study of embryos of another echinoderm (starfish) has reported that Six3 knockdown‐embryos still express foxQ2 at the gastrula stage (Cheatle Jarvela, Yankura, & Hinman, ), although it is possible that the regulatory relationship was modified after the diversification of sea urchin and starfish. In summary, it is still unclear how the expression of foxQ2 is positively regulated and maintained in the anterior neuroectoderm.…”